Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants

Abstract

Imidazoquinoline derivatives (IMDs) and related compounds function as synthetic agonists of Toll-like receptors 7 and 8 (TLR7/8) and one is FDA approved for topical antiviral and skin cancer treatments. Nevertheless, these innate immune system-activating drugs have potentially much broader therapeutic utility; they have been pursued as antitumor immunomodulatory agents and more recently as candidate vaccine adjuvants for cancer and infectious disease. The broad expression profiles of TLR7/8, poor pharmacokinetic properties of IMDs, and toxicities associated with systemic administration, however, are formidable barriers to successful clinical translation. Herein, we review IMD formulations that have advanced to the clinic and discuss issues related to biodistribution and toxicity that have hampered the further development of these compounds. Recent strategies aimed at enhancing safety and efficacy, particularly through the use of bioconjugates and nanoparticle formulations that alter pharmacokinetics, biodistribution, and cellular targeting, are described. Finally, key aspects of the biology of TLR7 signaling, such as TLR7 tolerance, that may need to be considered in the development of new IMD therapeutics are discussed.

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    Miyake K, Shibata T, Ohto U, Shimizu T, Emerging roles of the processing of nucleic acids and Toll-like receptors in innate immune responses to nucleic acids, J Leukocyte Biol. 101 (2017 ) 135–142..

    Not in our library10.1189/jlb.4mr0316-108r

92. 92.

    Maeda K, Akira S, TLR7 Structure: Cut in Z-Loop, Immunity. 45 (2016 ) 705–707..

    Not in our library10.1016/j.immuni.2016.10.003

93. 93.

    Sakaniwa K, Shimizu T, Targeting the innate immune receptor TLR8 using small-molecule agents, Acta Crystallogr Sect D Struct Biology. 76 (2020 ) 621–629..

    Not in our library10.1107/s2059798320006518

94. 94.

    Isobe Y, Kurimoto A, Tobe M, Hashimoto K, Nakamura T, Norimura K, Ogita H, Takaku H, Synthesis and Biological Evaluation of Novel 9-Substituted-8-Hydroxyadenine Derivatives as Potent Interferon Inducers, J Med Chem. 49 (2006 ) 2088–2095..

    Not in our library10.1021/jm051089s

95. 95.

    Roethle PA, McFadden RM, Yang H, Hrvatin P, Hui H, Graupe M, Gallagher B, Chao J, Hesselgesser J, Duatschek P, Zheng J, Lu B, Tumas DB, Perry J, Halcomb RL, Identification and Optimization of Pteridinone Toll-like Receptor 7 (TLR7) Agonists for the Oral Treatment of Viral Hepatitis, J Med Chem. 56 (2013 ) 7324–7333..

    Not in our library10.1021/jm400815m

96. 96.

    McGowan DC, Latest Advances in Small Molecule TLR 7/8 Agonist Drug Research, Curr Top Med Chem. 19 (2019 ) 2228–2238..

    Not in our library10.2174/1568026619666191009165418

97. 97.

    Patinote C, Karroum NB, Moarbess G, Cirnat N, Kassab I, Bonnet P-A, Deleuze-Masquéfa C, Agonist and antagonist ligands of toll-like receptors 7 and 8: Ingenious tools for therapeutic purposes, Eur J Med Chem. 193 (2020 ) 112238..

    Not in our library10.1016/j.ejmech.2020.112238

98. 98.

    Wang Y, Zhang S, Li H, Wang H, Zhang T, Hutchinson MR, Yin H, Wang X, Small-Molecule Modulators of Toll-like Receptors, Accounts Chem Res. 53 (2020 ) 1046–1055..

    Not in our library10.1021/acs.accounts.9b00631

99. 99.

    Kurimoto A, Tobe M, Ogita H, Ogino T, Takaku H, Ichii S, Kawakami H, Isobe Y, Prodrugs of 9-Benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine: Potent Interferon Inducing Agents in Monkeys, Chem Pharm Bull. 52 (2004 ) 466–469..

    Not in our library10.1248/cpb.52.466

100. 100.

     Nakamura T, Wada H, Kurebayashi H, McInally T, Bonnert R, Isobe Y, Synthesis and evaluation of 8-oxoadenine derivatives as potent Toll-like receptor 7 agonists with high water solubility, Bioorg Med Chem Lett. 23 (2013 ) 669–672..

     Not in our library10.1016/j.bmcl.2012.11.114

101. 101.

     Heil F, Ahmad-Nejad P, Hemmi H, Hochrein H, Ampenberger F, Gellert T, Dietrich H, Lipford G, Takeda K, Akira S, Wagner H, Bauer S, The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily, Eur J Immunol. 33 (2003 ) 2987–2997..

     Not in our library10.1002/eji.200324238

102. 102.

     Evans JT, Bess LS, Mwakwari SC, Livesay MT, Li Y, Cybulski V, Johnson DA, Bazin HG, Synthetic Toll-like Receptors 7 and 8 Agonists: Structure–Activity Relationship in the Oxoadenine Series, Acs Omega. 4 (2019 ) 15665–15677..

     Not in our library10.1021/acsomega.9b02138

103. 103.

     Bazin HG, Li Y, Khalaf JK, Mwakwari S, Livesay MT, Evans JT, Johnson DA, Structural requirements for TLR7-selective signaling by 9-(4-piperidinylalkyl)-8-oxoadenine derivatives., Bioorg Med Chem Lett. 25 (2015 ) 1318–23..

     Not in our library10.1016/j.bmcl.2015.01.037

104. 104.

     Weterings JJ, Khan S, van Noort G.J. van der H., Melief CJM, Overkleeft HS, van der Burg SH, Ossendorp F, van der Marel GA, Filippov DV, 2-Azidoalkoxy-7-hydro-8-oxoadenine derivatives as TLR7 agonists inducing dendritic cell maturation, Bioorg Med Chem Lett. 19 (2009 ) 2249–2251..

     Not in our library10.1016/j.bmcl.2009.02.095

105. 105.

     Yu H, Jin H, Sun L, Zhang L, Sun G, Wang Z, Yu Y, Toll-Like Receptor 7 Agonists: Chemical Feature Based Pharmacophore Identification and Molecular Docking Studies, Plos One. 8 (2013 ) e56514..

     Not in our library10.1371/journal.pone.0056514

106. 106.

     Harrison LI, Stoesz JD, Battiste JL, Nelson RJ, Zarraga IE, A pharmaceutical comparison of different commercially available imiquimod 5% cream products, J Dermatol Treat. 20 (2009 ) 160–164..

     Not in our library10.1080/09546630802513693

107. 107.

     Chollet JL, Jozwiakowski MJ, Phares KR, Reiter MJ, Roddy PJ, Schultz HJ, Ta QV, Tomai MA, Development of a Topically Active Imiquimod Formulation, Pharm Dev Technol. 4 (1999 ) 35–43..

     Not in our library10.1080/10837459908984222

108. 108.

     Sauder DN, Imiquimod: modes of action, Brit J Dermatol. 149 (2003 ) 5–8..

     Not in our library10.1046/j.0366-077x.2003.05628.x

109. 109.

     Samuel CE, Antiviral Actions of Interferons, Clin Microbiol Rev. 14 (2001 ) 778–809..

     Not in our library10.1128/cmr.14.4.778-809.2001

110. 110.

     Silverman RH, Viral Encounters with 2′,5′-Oligoadenylate Synthetase and RNase L during the Interferon Antiviral Response, J Virol. 81 (2007 ) 12720–12729..

     Not in our library10.1128/jvi.01471-07

111. 111.

     Palamara F, Meindl S, Holcmann M, Lührs P, Stingl G, Sibilia M, Identification and Characterization of pDC-Like Cells in Normal Mouse Skin and Melanomas Treated with Imiquimod, J Immunol. 173 (2004 ) 3051–3061..

     Not in our library10.4049/jimmunol.173.5.3051

112. 112.

     Vidal D, Topical Imiquimod: Mechanism of Action and Clinical Applications, Mini-Rev Med Chem. 6 (2006 ) 499–503..

     Not in our library10.2174/138955706776876131

113. 113.

     Beglin M, Melar-New M, Laimins L, Human papillomaviruses and the interferon response., J Interf Cytokine Res Official J Int Soc Interf Cytokine Res. 29 (2009 ) 629–35..

     Not in our library10.1089/jir.2009.0075

114. 114.

     Dahl MV, Imiquimod: A cytokine inducer, J Am Acad Dermatol. 47 (2002 ) S205–S208..

     Not in our library10.1067/mjd.2002.126586

115. 115.

     Suzuki H, Wang B, Shivji GM, Toto P, Amerio P, Sauder DN, Tomai MA, Miller RL, Imiquimod, a Topical Immune Response Modifier, Induces Migration of Langerhans Cells 1 1 The authors have declared a conflict of interest., J Invest Dermatol. 114 (2000 ) 135–141..

     Not in our library10.1046/j.1523-1747.2000.00833.x

116. 116.

     Perry CM, Lamb HM, Topical Imiquimod: A Review of its Use in Genital Warts, Drugs. 58 (1999 ) 375–390..

     Not in our library10.2165/00003495-199958020-00017

117. 117.

     Edwards L, Ferenczy A, Eron L, Baker D, Owens ML, Fox TL, Hougham AJ, Schmitt KA, Self-administered Topical 5% Imiquimod Cream for External Anogenital Warts, Arch Dermatol. 134 (1998 ) 25..

     Not in our library10.1001/archderm.134.1.25

118. 118.

     Deza G, Martin-Ezquerra G, Curto-Barredo L, García JV, Pujol RM, Successful treatment of hypertrophic herpes simplex genitalis in HIV-infected patient with topical imiquimod, J Dermatology. 42 (2015 ) 1176–1178..

     Not in our library10.1111/1346-8138.12969

119. 119.

     Miller RL, Imbertson LM, Reiter MJ, Gerster JF, Treatment of primary herpes simplex virus infection in guinea pigs by imiquimod, Antivir Res. 44 (1999 ) 31–42..

     Not in our library10.1016/s0166-3542(99)00052-2

120. 120.

     Schacker TW, Conant M, Thoming C, Stanczak T, Wang Z, Smith M, Imiquimod 5-Percent Cream Does Not Alter the Natural History of Recurrent Herpes Genitalis: a Phase II, Randomized, Double-Blind, Placebo-Controlled Study, Antimicrob Agents Ch. 46 (2002 ) 3243–3248..

     Not in our library10.1128/aac.46.10.3243-3248.2002

121. 121.

     Winters U, Daayana S, Lear JT, Tomlinson AE, Elkord E, Stern PL, Kitchener HC, Clinical and Immunologic Results of a Phase II Trial of Sequential Imiquimod and Photodynamic Therapy for Vulval Intraepithelial Neoplasia, Clin Cancer Res. 14 (2008 ) 5292–5299..

     Not in our library10.1158/1078-0432.ccr-07-4760

122. 122.
     Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia · 2010

     No notice
123. 123.

     Wouters T, Hendriks N, Koeneman M, Kruse A-J, van de Sande A, van Beekhuizen HJ, Gerestein KG, Bekkers RLM, Piek JMJ, Systemic adverse events in imiquimod use for cervical intraepithelial neoplasia – A case series, Case Reports Women’s Heal. 21 (2019 ) e00105..

     Not in our library10.1016/j.crwh.2019.e00105

124. 124.

     Hadley G, Derry S, Moore RA, Imiquimod for Actinic Keratosis: Systematic Review and Meta-Analysis, J Invest Dermatol. 126 (2006 ) 1251–1255..

     Not in our library10.1038/sj.jid.5700264

125. 125.

     Uhlenhake EE, Optimal treatment of actinic keratoses., Clin Interv Aging. 8 (2013 ) 29–35..

     Not in our library10.2147/cia.s31930

126. 126.

     Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, Lee JH, Fox TL, Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials, J Am Acad Dermatol. 50 (2004 ) 714–721..

     Not in our library10.1016/j.jaad.2003.12.010

127. 127.

     Geisse J, Caro I, Lindholm J, Golitz L, Stampone P, Owens M, Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies, J Am Acad Dermatol. 50 (2004 ) 722–733..

     Not in our library10.1016/j.jaad.2003.11.066

128. 128.

     Wysocka M, Newton S, Benoit BM, Introcaso C, Hancock AS, Chehimi J, Richardson SK, Gelfand JM, Montaner LJ, Rook AH, Synthetic Imidazoquinolines Potently and Broadly Activate the Cellular Immune Response of Patients with Cutaneous T-Cell Lymphoma: Synergy with Interferon-γ Enhances Production of Interleukin-12, Clin Lymphoma Myeloma. 7 (2007 ) 524–534..

     Not in our library10.3816/clm.2007.n.037

129. 129.

     Suchin KR, Junkins-Hopkins JM, Rook AH, Treatment of Stage IA Cutaneous T-Cell Lymphoma With Topical Application of the Immune Response Modifier Imiquimod, Arch Dermatol. 138 (2002 ) 1137..

     Not in our library10.1001/archderm.138.9.1137

130. 130.

     Rook AH, Gelfand JM, Wysocka M, Troxel AB, Benoit B, Surber C, Elenitsas R, Buchanan MA, Leahy DS, Watanabe R, Kirsch IR, Kim EJ, Clark RA, Topical resiquimod can induce disease regression and enhance T-cell effector functions in cutaneous T-cell lymphoma, Blood. 126 (2015 ) 1452–61..

     Not in our library10.1182/blood-2015-02-630335

131. 131.

     Wolf IH, Smolle J, Binder B, Cerroni L, Richtig E, Kerl H, Topical Imiquimod in the Treatment of Metastatic Melanoma to Skin, Arch Dermatol. 139 (2003 ) 273..

     Not in our library10.1001/archderm.139.3.273

132. 132.

     Narayan R, Nguyen H, Bentow JJ, Moy L, Lee DK, Greger S, Haskell J, Vanchinathan V, Chang P-L, Tsui S, Konishi T, Comin-Anduix B, Dauphine C, Vargas HI, Economou JS, Ribas A, Bruhn KW, Craft N, Immunomodulation by imiquimod in patients with high-risk primary melanoma., J Investigative Dermatology. 132 (2011 ) 163–9..

     Not in our library10.1038/jid.2011.247

133. 133.

     Adams S, Kozhaya L, Martiniuk F, Meng T-C, Chiriboga L, Liebes L, Hochman T, Shuman N, Axelrod D, Speyer J, Novik Y, Tiersten A, Goldberg JD, Formenti SC, Bhardwaj N, Unutmaz D, Demaria S, Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer., Clin Cancer Res Official J Am Assoc Cancer Res. 18 (2012 ) 6748–57..

     Not in our library10.1158/1078-0432.ccr-12-1149

134. 134.

     Campanelli A, Krischer J, Saurat J-H, Topical application of imiquimod and associated fever in children, J Am Acad Dermatol. 52 (2005 ) E1..

     Not in our library10.1016/j.jaad.2004.10.858

135. 135.

     Bauza A, Pozo LJD, Saus C, Martin A, Pemphigus-like lesions induced by imiquimod, Clin Exp Dermatol. 34 (2009 ) e60–e62..

     Not in our library10.1111/j.1365-2230.2008.03181.x

136. 136.

     Kumar B, Narang T, Local and systemic adverse effects to topical imiquimod due to systemic immune stimulation, Sex Transm Infect. 87 (2011 ) 432–432..

     Not in our library10.1136/sextrans-2011-050025

137. 137.

     Borden EC, Interferons α and β in cancer: therapeutic opportunities from new insights, Nat Rev Drug Discov. 18 (2019 ) 219–234..

     Not in our library10.1038/s41573-018-0011-2

138. 138.
     Anti-tumor Activity of Toll-Like Receptor 7 Agonists · 2017

     No notice
139. 139.

     Schon M, Bong AB, Drewniok C, Herz J, Geilen CC, Reifenberger J, Benninghoff B, Slade HB, Gollnick H, Schon MP, Tumor-Selective Induction of Apoptosis and the Small-Molecule Immune Response Modifier Imiquimod, Jnci J National Cancer Inst. 95 (2003 ) 1138–1149..

     Not in our library10.1093/jnci/djg016

140. 140.

     Huang S-W, Chang S-H, Mu S-W, Jiang H-Y, Wang S-T, Kao J-K, Huang J-L, Wu C-Y, Chen Y-J, Shieh J-J, Imiquimod activates p53-dependent apoptosis in a human basal cell carcinoma cell line., J Dermatol Sci. 81 (2015 ) 182–91..

     Not in our library10.1016/j.jdermsci.2015.12.011

141. 141.

     Dajon M, Iribarren K, Cremer I, Dual roles of TLR7 in the lung cancer microenvironment, Oncoimmunology. 4 (2015 ) e991615..

     Not in our library10.4161/2162402x.2014.991615

142. 142.

     Schön MP, Schön M, TLR7 and TLR8 as targets in cancer therapy, Oncogene. 27 (2008 ) 190–199..

     Not in our library10.1038/sj.onc.1210913

143. 143.

     Smits ELJM, Ponsaerts P, Berneman ZN, Tendeloo VFIV, The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy, Oncol. 13 (2008 ) 859–875..

     Not in our library10.1634/theoncologist.2008-0097

144. 144.

     Harrison LI, Astry C, Kumar S, Yunis C, Pharmacokinetics of 852A, an Imidazoquinoline Toll-Like Receptor 7-Specific Agonist, Following Intravenous, Subcutaneous, and Oral Administrations in Humans, J Clin Pharmacol. 47 (2007 ) 962–969..

     Not in our library10.1177/0091270007303766

145. 145.

     Dudek AZ, Yunis C, Harrison LI, Kumar S, Hawkinson R, Cooley S, Vasilakos JP, Gorski KS, Miller JS, First in Human Phase I Trial of 852A, a Novel Systemic Toll-like Receptor 7 Agonist, to Activate Innate Immune Responses in Patients with Advanced Cancer, Clin Cancer Res. 13 (2007 ) 7119–7125..

     Not in our library10.1158/1078-0432.ccr-07-1443

146. 146.

     Dummer R, Hauschild A, Becker JC, Grob J-J, Schadendorf D, Tebbs V, Skalsky J, Kaehler KC, Moosbauer S, Clark R, Meng T-C, Urosevic M, An Exploratory Study of Systemic Administration of the Toll-like Receptor-7 Agonist 852A in Patients with Refractory Metastatic Melanoma, Clin Cancer Res. 14 (2008 ) 856–864..

     Not in our library10.1158/1078-0432.ccr-07-1938

147. 147.

     Pope BL, Chourmouzis E, Victorino L, MacIntyre JP, Capetola RJ, Lau CY, Loxoribine (7-allyl-8-oxoguanosine) activates natural killer cells and primes cytolytic precursor cells for activation by IL-2., J Immunol Baltim Md 1950. 151 (1993 ) 3007–17.

     Not in our library

148. 148.

     Pope BL, Sigindere J, Chourmouzis E, MacIntyre P, Goodman MG, 7-Allyl-8-oxoguanosine (loxoribine) inhibits the metastasis of B16 melanoma cells and has adjuvant activity in mice immunized with a B16 tumor vaccine, Cancer Immunol Immunother. 38 (1994 ) 83–91..

     Not in our library10.1007/bf01526202

149. 149.

     Agarwala SS, Kirkwood JM, Bryant J, Phase I, Randomized, Double-blind Trial of 7-allyl-8-oxoguanosine (Loxoribine) in Advanced Cancer, Cytokines Cell Mol Ther. 6 (2009 ) 171–176..

     Not in our library10.1080/mccm.6.4.171.176

150. 150.

     Adlard AL, Dovedi SJ, Telfer BA, Koga-Yamakawa E, Pollard C, Honeychurch J, Illidge TM, Murata M, Robinson DT, Jewsbury PJ, Wilkinson RW, Stratford IJ, A novel systemically administered toll-like receptor 7 agonist potentiates the effect of ionizing radiation in murine solid tumor models, Int J Cancer. 135 (2014 ) 820–9..

     Not in our library10.1002/ijc.28711

151. 151.

     Disis ML, Bernhard H, Jaffee EM, Use of tumour-responsive T cells as cancer treatment., Lancet Lond Engl. 373 (2009 ) 673–83..

     Not in our library10.1016/s0140-6736(09)60404-9

152. 152.
     Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy · 2018

     No notice
153. 153.

     Lu H, TLR Agonists for Cancer Immunotherapy: Tipping the Balance between the Immune Stimulatory and Inhibitory Effects, Front Immunol. 5 (2014 ) 83..

     Not in our library10.3389/fimmu.2014.00083

154. 154.

     Ota Y, Otsubo T, Koroki J, Hirose Y, Koga-Yamakawa E, Murata M, Goto M, Matsuki Y, Abstract 4726: Novel intravenous injectable TLR7 agonist, DSP-0509, synergistically enhanced antitumor immune responses in combination with anti-PD-1 antibody, (2018 ) 4726–4726..

     Not in our library10.1158/1538-7445.am2018-4726

155. 155.

     Ackerman SE, Gonzalez JC, Gregorio JD, Paik JC, Hartmann FJ, Kenkel JA, Lee A, Luo A, Pearson CI, Nguyen ML, Ackerman B, Sheu LY, Laura RP, Chapin SJ, Safina BS, Bendall SC, Dornan D, Engleman EG, Alonso MN, Abstract 1559: TLR7/8 immune-stimulating antibody conjugates elicit robust myeloid activation leading to enhanced effector function and anti-tumor immunity in pre-clinical models, (2019 ) 1559–1559..

     Not in our library10.1158/1538-7445.am2019-1559

156. 156.

     Ackerman SE, Pearson CI, Gregorio JD, Gonzalez JC, Kenkel JA, Hartmann FJ, Luo A, Ho PY, LeBlanc H, Blum LK, Kimmey SC, Luo A, Nguyen ML, Paik JC, Sheu LY, Ackerman B, Lee A, Li H, Melrose J, Laura RP, Ramani VC, Henning KA, Jackson DY, Safina BS, Yonehiro G, Devens BH, Carmi Y, Chapin SJ, Bendall SC, Kowanetz M, Dornan D, Engleman EG, Alonso MN, Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity, Nat Cancer. (2020 ) 1–16..

     Not in our library10.1038/s43018-020-00136-x

157. 157.

     Metz H, Childs M, Brevik J, Winship D, Brender T, Comeau M, Moyes K, Chang J, Adamo J, Setter B, Xu H, Fan L-Q, Smith S, Tan P, DuBose R, Latchman Y, Baum P, Odegard V, SBT6050, a HER2-directed TLR8 therapeutic, as a systemically administered, tumor-targeted human myeloid cell agonist., J Clin Oncol. 38 (2020 ) 3110–3110..

     Not in our library10.1200/jco.2020.38.15_suppl.3110

158. 158.

     Moyes K, Brender T, Smith SW, Xu H, Setter B, Fan L-Q, Brunette R, Killebrew J, Tan P, Coburn C, Baum P, Odegard V, Abstract 3271: A systemically administered, conditionally active TLR8 agonist for the treatment of HER2-expressing tumors, (2019 ) 3271–3271..

     Not in our library10.1158/1538-7445.am2019-3271

159. 159.

     Tan J, Harding T, Fletcher S, Fish S, Haley G, Lennox J, Rueden E, D.A. and Appleman J, The active metabolite of the TLR7 agonist prodrug ANA773 activates anti-tumor activity by natural killer cells, Cancer Res. 67 (9 Supplement) (1AD) 3556. https://cancerres-aacrjournals-org.libproxy.mit.edu/content/67/9_Supplement/3556.

     Not in our library

160. 160.

     Daniels GA, Carson WE, Mita AC, Kendra KL, Rahimy MH, Inman DW, Appleman JR, Freddo JL, McNeel DG, Phase I open-label, dose-escalation study of ANA773 tosylate, an oral prodrug of a toll-like receptor-7 agonist, in patients with advanced solid tumors., J Clin Oncol. 29 (2011 ) 2524–2524..

     Not in our library10.1200/jco.2011.29.15_suppl.2524

161. 161.

     Witjes WPJ, K&oumlnig M, Boeminghaus FP, Hall RR, Schulman CC, Zurlo M, Fittipaldo A, Riggi M, Debruyne FMJ, Results of a European Comparative Randomized Study Comparing Oral Bropirimine versus Intravesical BCG Treatment in BCG-Naive Patients with Carcinoma in situ of the Urinary Bladder, Eur Urol. 36 (1999 ) 576–581..

     Not in our library10.1159/000020051

162. 162.

     Appleman JR, Webber SE, Pharmacodynamic response in vitro and in vivo of novel orally administered Toll-like Receptor 7 agonists for systemic immunotherapy of cancer, in: Pharmacodynamic Response in Vitro and in Vivo of Novel Orally Administered Toll-like Receptor 7 Agonists for Systemic Immunotherapy of Cancer, 2019.

     Not in our library

163. 163.

     Wu TY-H, Strategies for designing synthetic immune agonists, Immunology. 148 (2016 ) 315–325..

     Not in our library10.1111/imm.12622

164. 164.

     Hayashi T, Crain B, Corr M, Chan M, Cottam HB, Maj R, Barberis A, Leoni L, Carson DA, Intravesical Toll-like receptor 7 agonist R-837: Optimization of its formulation in an orthotopic mouse model of bladder cancer, Int J Urol. 17 (2010 ) 483–490..

     Not in our library10.1111/j.1442-2042.2010.02503.x

165. 165.

     Arends TJH, Lammers RJM, Falke J, van der Heijden AG, Rustighini I, Pozzi R, Ravic M, Eisenhardt A, Vergunst H, Witjes JA, Pharmacokinetic, Pharmacodynamic, and Activity Evaluation of TMX-101 in a Multicenter Phase 1 Study in Patients With Papillary Non-Muscle-Invasive Bladder Cancer, Clin Genitourin Canc. 13 (2015 ) 204–209.e2..

     Not in our library10.1016/j.clgc.2014.12.010

166. 166.

     Donin NM, Chamie K, Lenis AT, Pantuck AJ, Reddy M, Kivlin D, Holldack J, Pozzi R, Hakim G, Karsh LI, Lamm DL, Belkoff LH, Belldegrun AS, Holden S, Shore N, A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer, Urologic Oncol Seminars Orig Investigations. 35 (2017 ) 39.e1–39.e7..

     Not in our library10.1016/j.urolonc.2016.09.006

167. 167.

     Northfelt DW, Ramanathan RK, Cohen PA, Hoff DDV, Weiss GJ, Dietsch GN, Manjarrez KL, Randall TD, Hershberg RM, A Phase I Dose-Finding Study of the Novel Toll-like Receptor 8 Agonist VTX-2337 in Adult Subjects with Advanced Solid Tumors or Lymphoma, Clin Cancer Res. 20 (2014 ) 3683–3691..

     Not in our library10.1158/1078-0432.ccr-14-0392

168. 168.

     Facciabene A, Malykhin A, Mathews M, Fang C, Dietsch G, Hershberg R, Coukos G, Abstract 4745: TLR8 agonist and Doxil chemotherapy potently activate human antitumor immune response in a human immune system mouse model, (2011 ) 4745–4745..

     Not in our library10.1158/1538-7445.am2011-4745

169. 169.

     Dietsch GN, Randall TD, Gottardo R, Northfelt DW, Ramanathan RK, Cohen PA, Manjarrez KL, Newkirk M, Bryan JK, Hershberg RM, Late-Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337), Clin Cancer Res. 21 (2015 ) 5445–5452..

     Not in our library10.1158/1078-0432.ccr-15-0578

170. 170.

     Singh M, Khong H, Dai Z, Huang X-F, Wargo JA, Cooper ZA, Vasilakos JP, Hwu P, Overwijk WW, Effective innate and adaptive antimelanoma immunity through localized TLR7/8 activation., J Immunol Baltim Md 1950. 193 (2014 ) 4722–31..

     Not in our library10.4049/jimmunol.1401160

171. 171.

     Brown TD, Whitehead KA, Mitragotri S, Materials for oral delivery of proteins and peptides, Nat Rev Mater. 5 (2019 ) 127–148..

     Not in our library10.1038/s41578-019-0156-6

172. 172.

     Patel MC, Shirey KA, Pletneva LM, Boukhvalova MS, Garzino-Demo A, Vogel SN, Blanco JC, Novel drugs targeting Toll-like receptors for antiviral therapy, Future Virol. 9 (2014 ) 811–829..

     Not in our library10.2217/fvl.14.70

173. 173.

     Horscroft NJ, Pryde DC, Bright H, Antiviral applications of Toll-like receptor agonists, J Antimicrob Chemoth. 67 (2012 ) 789–801..

     Not in our library10.1093/jac/dkr588

174. 174.

     Melchjorsen J, Learning from the messengers: innate sensing of viruses and cytokine regulation of immunity - clues for treatments and vaccines., Viruses. 5 (2013 ) 470–527..

     Not in our library10.3390/v5020470

175. 175.

     Pockros PJ, Guyader D, Patton H, Tong MJ, Wright T, McHutchison JG, Meng T-C, Oral resiquimod in chronic HCV infection: Safety and efficacy in 2 placebo-controlled, double-blind phase IIa studies, Journal of Hepatology. 47 (2007 ) 174–82..

     Not in our library10.1016/j.jhep.2007.02.025

176. 176.

     Fidock MD, Souberbielle BE, Laxton C, Rawal J, Delpuech-Adams O, Corey TP, Colman P, Kumar V, Cheng JB, Wright K, Srinivasan S, Rana K, Craig C, Horscroft N, Perros M, Westby M, Webster R, van der Ryst E, The innate immune response, clinical outcomes, and ex vivo HCV antiviral efficacy of a TLR7 agonist (PF-4878691)., Clin Pharmacol Ther. 89 (2011 ) 821–9..

     Not in our library10.1038/clpt.2011.60

177. 177.

     Xiang AX, Webber SE, Kerr BM, Rueden EJ, Lennox JR, Haley GJ, Wang T, Ng JS, Herbert MR, Clark DL, Banh VN, Li W, Fletcher SP, Steffy KR, Bartkowski DM, Kirkovsky LI, Bauman LA, Averett DR, Discovery of ANA975: An Oral Prodrug of the TLR-7 Agonist Isatoribine, Nucleosides Nucleotides Nucleic Acids. 26 (2007 ) 635–640..

     Not in our library10.1080/15257770701490472

178. 178.

     Suslov A, Wieland S, Menne S, Modulators of innate immunity as novel therapeutics for treatment of chronic hepatitis B, Curr Opin Virol. 30 (2018 ) 9–17..

     Not in our library10.1016/j.coviro.2018.01.008

179. 179.

     Miller RL, Meng T-C, Tomai MA, The antiviral activity of toll-like receptor 7 and 7/8 agonists, Drug News Perspect. 21 (2008 ) 69..

     Not in our library10.1358/dnp.2008.21.2.1188193

180. 180.

     Luk A, Jiang Q, Glavini K, Triyatni M, Zhao N, Racek T, Zhu Y, Grippo JF, A Single and Multiple Ascending Dose Study of Toll-Like Receptor 7 Agonist (RO7020531) in Chinese Healthy Volunteers, Clin Transl Sci. (2020 )..

     Not in our library10.1111/cts.12791

181. 181.

     Grippo JF, Folitar I, Passe S, Jiang Q, Rodriguez I, Fettner SH, Calleja E, Safety, tolerability, pharmacokinetics and pharmacodynamics of a TLR7 agonist prodrug RO6870868 in healthy volunteers, Clin Transl Sci. (2021 )..

     Not in our library10.1111/cts.13016

182. 182.

     Zhang H, Hu Y, Wu M, Liu J, Li X, Zhu X, Li C, Chen H, Liu C, Niu J, Ding Y, Safety, Pharmacokinetics, and Pharmacodynamics of TQ-A3334, an Oral Toll-Like Receptor 7 Agonist, in Healthy Individuals, Expert Opin Inv Drug. (2021 )..

     Not in our library10.1080/13543784.2021.1873275

183. 183.

     Gao L, Dai L, Yu Y, Gu L, Zhao J, Ji Y, Yun H, Zhu W, Young J, O-015: Combination treatment of a TLR7 agonist RO7020531 and a capsid assembly modulator RO7049389 achieved sustainable viral load suppression and HBsAg loss in an AAV-HBV mouse model, J Viral Hepatitis. 25 (2018 ) 12–12..

     Not in our library10.1111/jvh.12_12922

184. 184.

     Fosdick A, Zheng J, Pflanz S, Frey CR, Hesselgesser J, Halcomb RL, Wolfgang G, Tumas DB, Pharmacokinetic and Pharmacodynamic Properties of GS-9620, a Novel Toll-Like Receptor 7 Agonist, Demonstrate Interferon-Stimulated Gene Induction without Detectable Serum Interferon at Low Oral Doses, J Pharmacol Exp Ther. 348 (2014 ) 96–105..

     Not in our library10.1124/jpet.113.207878

185. 185.

     Gane EJ, Lim Y-S, Gordon SC, Visvanathan K, Sicard E, Fedorak RN, Roberts S, Massetto B, Ye Z, Pflanz S, Garrison KL, Gaggar A, Subramanian GM, McHutchison JG, Kottilil S, Freilich B, Coffin CS, Cheng W, Kim YJ, The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection, J Hepatol. 63 (2015 ) 320–328..

     Not in our library10.1016/j.jhep.2015.02.037

186. 186.

     Menne S, Tumas DB, Liu KH, Thampi L, AlDeghaither D, Baldwin BH, Bellezza CA, Cote PJ, Zheng J, Halcomb R, Fosdick A, Fletcher SP, Daffis S, Li L, Yue P, Wolfgang GHI, Tennant BC, Sustained efficacy and seroconversion with the Toll-like receptor 7 agonist GS-9620 in the Woodchuck model of chronic hepatitis B., J Hepatol. 62 (2015 ) 1237–45..

     Not in our library10.1016/j.jhep.2014.12.026

187. 187.

     Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM, Fosdick A, Frey CR, Zheng J, Wolfgang G, Halcomb RL, Tumas DB, GS-9620, an Oral Agonist of Toll-Like Receptor-7, Induces Prolonged Suppression of Hepatitis B Virus in Chronically Infected Chimpanzees, Gastroenterology. 144 (2013 ) 1508–1517.e10..

     Not in our library10.1053/j.gastro.2013.02.003

188. 188.

     Korolowizc KE, Li B, Huang X, Yon C, Rodrigo E, Corpuz M, Plouffe DM, Kallakury BV, Suresh M, Wu TY-H, Miller AT, Menne S, Liver-Targeted Toll-Like Receptor 7 Agonist Combined With Entecavir Promotes a Functional Cure in the Woodchuck Model of Hepatitis B Virus, Hepatology Commun. 3 (2019 ) 1296–1310..

     Not in our library10.1002/hep4.1397

189. 189.
     Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver · 2014

     No notice
190. 190.

     Guidotti LG, Rochford R, Chung J, Shapiro M, Purcell R, Chisari FV, Viral Clearance Without Destruction of Infected Cells During Acute HBV Infection, Science. 284 (1999 ) 825–829..

     Not in our library10.1126/science.284.5415.825

191. 191.

     Mackman RL, Mish M, Chin G, Perry JK, Appleby T, Aktoudianakis V, Metobo S, Pyun P, Niu C, Daffis S, Yu H, Zheng J, Villasenor AG, Zablocki J, Chamberlain J, Jin H, Lee G, Suekawa-Pirrone K, Santos R, Delaney WE, Fletcher SP, Discovery of GS-9688 (Selgantolimod) as a Potent and Selective Oral Toll-Like Receptor 8 Agonist for the Treatment of Chronic Hepatitis B, J Med Chem. (2020 )..

     Not in our library10.1021/acs.jmedchem.0c00100

192. 192.

     Daffis S, Balsitis S, Chamberlain J, Zheng J, Santos R, Rowe W, Ramakrishnan D, Pattabiraman D, Spurlock S, Chu R, Kang D, Mish M, Ramirez R, Li L, Li B, Ma S, Hung M, Voitenleitner C, Yon C, Suresh M, Menne S, Cote P, Delaney WE, Mackman R, Fletcher SP, Toll-Like Receptor 8 Agonist GS-9688 Induces Sustained Efficacy in the Woodchuck Model of Chronic Hepatitis B, Hepatology. (2020 )..

     Not in our library10.1002/hep.31255

193. 193.

     Bam RA, Hansen D, Irrinki A, Mulato A, Jones GS, Hesselgesser J, Frey CR, Cihlar T, Yant SR, TLR7 Agonist GS-9620 Is a Potent Inhibitor of Acute HIV-1 Infection in Human Peripheral Blood Mononuclear Cells, Antimicrob Agents Ch. 61 (2017 ) e01369–16..

     Not in our library10.1128/aac.01369-16

194. 194.

     Borducchi EN, Cabral C, Stephenson KE, Liu J, Abbink P, Ng’ang’a D, Nkolola JP, Brinkman AL, Peter L, Lee BC, Jimenez J, Jetton D, Mondesir J, Mojta S, Chandrashekar A, Molloy K, Alter G, Gerold JM, Hill AL, Lewis MG, Pau MG, Schuitemaker H, Hesselgesser J, Geleziunas R, Kim JH, Robb ML, Michael NL, Barouch DH, Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys, Nature. 540 (2016 ) 284–287..

     Not in our library10.1038/nature20583

195. 195.

     Borducchi EN, Liu J, Nkolola JP, Cadena AM, Yu W-H, Fischinger S, Broge T, Abbink P, Mercado NB, Chandrashekar A, Jetton D, Peter L, McMahan K, Moseley ET, Bekerman E, Hesselgesser J, Li W, Lewis MG, Alter G, Geleziunas R, Barouch DH, Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys, Nature. 563 (2018 ) 360–364..

     Not in our library10.1038/s41586-018-0600-6

196. 196.

     Lim S-Y, Osuna CE, Hraber PT, Hesselgesser J, Gerold JM, Barnes TL, Sanisetty S, Seaman MS, Lewis MG, Geleziunas R, Miller MD, Cihlar T, Lee WA, Hill AL, Whitney JB, TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy, Sci Transl Med. 10 (2018 ) eaao4521..

     Not in our library10.1126/scitranslmed.aao4521

197. 197.

     Eigenbrod T, Dalpke AH, Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses, J Immunol. 195 (2015 ) 411–418..

     Not in our library10.4049/jimmunol.1500530

198. 198.

     Moen SH, Ehrnström B, Kojen JF, Yurchenko M, Beckwith KS, Afset JE, Damås JK, Hu Z, Yin H, Espevik T, Stenvik J, Human Toll-like Receptor 8 (TLR8) Is an Important Sensor of Pyogenic Bacteria, and Is Attenuated by Cell Surface TLR Signaling, Front Immunol. 10 (2019 ) 1209..

     Not in our library10.3389/fimmu.2019.01209

199. 199.

     Cervantes JL, Weinerman B, Basole C, Salazar JC, TLR8: the forgotten relative revindicated, Cell Mol Immunol. 9 (2012 ) 434–438..

     Not in our library10.1038/cmi.2012.38

200. 200.

     Dowling DJ, van Haren SD, Scheid A, Bergelson I, Kim D, Mancuso CJ, Foppen W, Ozonoff A, Fresh L, Theriot TB, Lackner AA, Fichorova RN, Smirnov D, Vasilakos JP, Beaurline JM, Tomai MA, Midkiff CC, Alvarez X, Blanchard JL, Gilbert MH, Aye PP, Levy O, TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth., Jci Insight. 2 (2017 ) e91020..

     Not in our library10.1172/jci.insight.91020

201. 201.

     Dowling DJ, Recent Advances in the Discovery and Delivery of TLR7/8 Agonists as Vaccine Adjuvants, Immunohorizons. 2 (2018 ) 185–197..

     Not in our library10.4049/immunohorizons.1700063

202. 202.

     Abt MC, Buffie CG, Sušac B, Becattini S, Carter RA, Leiner I, Keith JW, Artis D, Osborne LC, Pamer EG, TLR-7 activation enhances IL-22–mediated colonization resistance against vancomycin-resistant enterococcus, Sci Transl Med. 8 (2016 ) 327ra25–327ra25..

     Not in our library10.1126/scitranslmed.aad6663

203. 203.

     Drake MG, Kaufman EH, Fryer AD, Jacoby DB, The Therapeutic Potential of Toll-Like Receptor 7 Stimulation in Asthma, Inflamm Allergy-Drug Targets. 11 (2012 ) 484–491..

     Not in our library10.2174/187152812803589967

204. 204.

     Lebold KM, Jacoby DB, Drake MG, Toll-Like Receptor 7-Targeted Therapy in Respiratory Disease, Transfus Med Hemoth. 43 (2016 ) 114–119..

     Not in our library10.1159/000445324

205. 205.

     Adner M, Starkhammar M, Georén SK, Dahlén S-E, Cardell L-O, Toll-like receptor (TLR) 7 decreases and TLR9 increases the airway responses in mice with established allergic inflammation, Eur J Pharmacol. 718 (2013 ) 544–551..

     Not in our library10.1016/j.ejphar.2013.09.004

206. 206.

     Kline JN, Immunotherapy of asthma using CpG oligodeoxynucleotides, Immunol Res. 39 (2007 ) 279–286..

     Not in our library10.1007/s12026-007-0083-2

207. 207.

     Barnes PJ, New drugs for asthma, Nat Rev Drug Discov. 3 (2004 ) 831–844..

     Not in our library10.1038/nrd1524

208. 208.

     Drake MG, Scott GD, Proskocil BJ, Fryer AD, Jacoby DB, Kaufman EH, Toll-like Receptor 7 Rapidly Relaxes Human Airways, Am J Resp Crit Care. 188 (2013 ) 664–672..

     Not in our library10.1164/rccm.201303-0442oc

209. 209.

     Ellis AK, Tsitoura DC, Quint D, Powley W, Lee LA, Safety and pharmacodynamics of intranasal GSK2245035, a TLR7 agonist for allergic rhinitis: A randomized trial, Clin Exp Allergy. 47 (2017 ) 1193–1203..

     Not in our library10.1111/cea.12974

210. 210.

     Biggadike K, Ahmed M, Ball DI, Coe DM, Wilk DAD, Edwards CD, Gibbon BH, Hardy CJ, Hermitage SA, Hessey JO, Hillegas AE, Hughes SC, Lazarides L, Lewell XQ, Lucas A, Mallett DN, Price MA, Priest FM, Quint DJ, Shah P, Sitaram A, Smith SA, Stocker R, Trivedi NA, Tsitoura DC, Weller V, Discovery of 6-Amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (GSK2245035), a Highly Potent and Selective Intranasal Toll-Like Receptor 7 Agonist for the Treatment of Asthma., J Med Chem. 59 (2016 ) 1711–26..

     Not in our library10.1021/acs.jmedchem.5b01647

211. 211.

     Biffen M, Matsui H, Edwards S, Leishman A, Eiho K, Holness E, Satterthwaite G, Doyle I, Wada H, Fraser N, Hawkins S, Aoki M, Tomizawa H, Benjamin A, Takaku H, McInally T, Murray C, Biological characterization of a novel class of toll-like receptor 7 agonists designed to have reduced systemic activity, Brit J Pharmacol. 166 (2012 ) 573–586..

     Not in our library10.1111/j.1476-5381.2011.01790.x

212. 212.

     Leaker BR, Singh D, Lindgren S, Almqvist G, Eriksson L, Young B, O’Connor B, Effects of the Toll-like receptor 7 (TLR7) agonist, AZD8848, on allergen-induced responses in patients with mild asthma: a double-blind, randomised, parallel-group study, Respir Res. 20 (2019 ) 288..

     Not in our library10.1186/s12931-019-1252-2

213. 213.

     Royer CM, Rudolph K, Dietsch GN, Hershberg RM, Barrett EG, VTX-1463, a novel TLR-8 agonist, attenuates nasal congestion after ragweed challenge in sensitized beagle dogs., Immun Inflamm Dis. 4 (2015 ) 45–51..

     Not in our library10.1002/iid3.91

214. 214.

     Horak F, VTX-1463, a novel TLR8 agonist for the treatment of allergic rhinitis., Expert Opin Inv Drug. 20 (2011 ) 981–6..

     Not in our library10.1517/13543784.2011.583237

215. 215.

     Blander J, Medzhitov R, On regulation of phagosome maturation and antigen presentation, Nat Immunol. 7 (2006 ) 1029–1035..

     Not in our library10.1038/ni1006-1029

216. 216.

     Wille-Reece U, Wu C, Flynn BJ, Kedl RM, Seder RA, Immunization with HIV-1 Gag Protein Conjugated to a TLR7/8 Agonist Results in the Generation of HIV-1 Gag-Specific Th1 and CD8+ T Cell Responses, J Immunol. 174 (2005 ) 7676–7683..

     Not in our library10.4049/jimmunol.174.12.7676

217. 217.

     Wille-Reece U, Flynn BJ, Loré K, Koup RA, Kedl RM, Mattapallil JJ, Weiss WR, Roederer M, Seder RA, HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates, Proc National Acad Sci. 102 (2005 ) 15190–15194..

     Not in our library10.1073/pnas.0507484102

218. 218.

     Kastenmüller K, Wille-Reece U, Lindsay RWB, Trager LR, Darrah PA, Flynn BJ, Becker MR, Udey MC, Clausen BE, Igyarto BZ, Kaplan DH, Kastenmüller W, Germain RN, Seder RA, Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets, J Clin Investigation. 121 (2011 ) 1782–96..

     Not in our library10.1172/jci45416

219. 219.

     Oh JZ, Kedl RM, The Capacity To Induce Cross-Presentation Dictates the Success of a TLR7 Agonist-Conjugate Vaccine for Eliciting Cellular Immunity, J Immunol Baltim Md 1950. 185 (2010 ) 4602–8..

     Not in our library10.4049/jimmunol.1001892

220. 220.

     Feng Y, Forsell MNE, Flynn B, Adams W, Loré K, Seder R, Wyatt RT, Hedestam GBK, Chemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation compromises recognition of conserved antigenic determinants, Virology. 446 (2013 ) 56–65..

     Not in our library10.1016/j.virol.2013.07.028

221. 221.

     Vecchi S, Bufali S, Uno T, Wu T, Arcidiacono L, Filippini S, Rigat F, O’Hagan D, Conjugation of a TLR7 agonist and antigen enhances protection in the S. pneumoniae murine infection model., European J Pharm Biopharm Official J Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E V. 87 (2014 ) 310–7..

     Not in our library10.1016/j.ejpb.2014.01.002

222. 222.

     Holbrook BC, Kim JR, Blevins LK, Jorgensen MJ, Kock ND, D’Agostino RB, Aycock ST, Hadimani MB, King SB, Parks GD, Alexander-Miller MA, A Novel R848-Conjugated Inactivated Influenza Virus Vaccine Is Efficacious and Safe in a Neonate Nonhuman Primate Model, J Immunol Baltim Md 1950. 197 (2016 ) 555–64..

     Not in our library10.4049/jimmunol.1600497

223. 223.

     Holbrook BC, Aycock ST, Machiele E, Clemens E, Gries D, Jorgensen MJ, Hadimani MB, King SB, Alexander-Miller MA, An R848 adjuvanted influenza vaccine promotes early activation of B cells in the draining lymph nodes of non-human primate neonates, Immunology. 153 (2018 ) 357–367..

     Not in our library10.1111/imm.12845

224. 224.

     Holbrook BC, D’Agostino RB, Aycock ST, Jorgensen MJ, Hadimani MB, King SB, Alexander-Miller MA, Adjuvanting an inactivated influenza vaccine with conjugated R848 improves the level of antibody present at 6months in a nonhuman primate neonate model, Vaccine. 35 (2017 ) 6137–6142..

     Not in our library10.1016/j.vaccine.2017.09.054

225. 225.

     Westcott MM, Clemens EA, Holbrook BC, King SB, Alexander-Miller MA, The choice of linker for conjugating R848 to inactivated influenza virus determines the stimulatory capacity for innate immune cells, Vaccine. 36 (2018 ) 1174–1182..

     Not in our library10.1016/j.vaccine.2018.01.035

226. 226.

     Lynn GM, Sedlik C, Baharom F, Zhu Y, Ramirez-Valdez RA, Coble VL, Tobin K, Nichols SR, Itzkowitz Y, Zaidi N, Gammon JM, Blobel NJ, Denizeau J, de la Rochere P, Francica BJ, Decker B, Maciejewski M, Cheung J, Yamane H, Smelkinson MG, Francica JR, Laga R, Bernstock JD, Seymour LW, Drake CG, Jewell CM, Lantz O, Piaggio E, Ishizuka AS, Seder RA, Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens, Nat Biotechnol. (2020 ) 1–13..

     Not in our library10.1038/s41587-019-0390-x

227. 227.

     Baharom F, Ramirez-Valdez RA, Tobin KKS, Yamane H, Dutertre C-A, Khalilnezhad A, Reynoso GV, Coble VL, Lynn GM, Mulè MP, Martins AJ, Finnigan JP, Zhang XM, Hamerman JA, Bhardwaj N, Tsang JS, Hickman HD, Ginhoux F, Ishizuka AS, Seder RA, Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells, Nat Immunol. (2020 ) 1–12..

     Not in our library10.1038/s41590-020-00810-3

228. 228.

     Wilson DS, Hirosue S, Raczy MM, Bonilla-Ramirez L, Jeanbart L, Wang R, Kwissa M, Franetich J-F, Broggi MAS, Diaceri G, Quaglia-Thermes X, Mazier D, Swartz MA, Hubbell JA, Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity, Nat Mater. 18 (2019 ) 175–185..

     Not in our library10.1038/s41563-018-0256-5

229. 229.

     Lynn GM, Laga R, Darrah PA, Ishizuka AS, Balaci AJ, Dulcey AE, Pechar M, Pola R, Gerner MY, Yamamoto A, Buechler CR, Quinn KM, Smelkinson MG, Vanek O, Cawood R, Hills T, Vasalatiy O, Kastenmüller K, Francica JR, Stutts L, Tom JK, Ryu KA, Esser-Kahn AP, Etrych T, Fisher KD, Seymour LW, Seder RA, In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity, Nature Biotechnology. 33 (2015 ) 1201–1210..

     Not in our library10.1038/nbt.3371

230. 230.

     Lynn GM, Chytil P, Francica JR, Lagová A, Kueberuwa G, Ishizuka AS, Zaidi N, Ramirez-Valdez RA, Blobel NJ, Baharom F, Leal J, Wang AQ, Gerner MY, Etrych T, Ulbrich K, Seymour LW, Seder RA, Laga R, Impact of Polymer-TLR-7/8 Agonist (Adjuvant) Morphology on the Potency and Mechanism of CD8 T Cell Induction, Biomacromolecules. 20 (2019 ) 854–870..

     Not in our library10.1021/acs.biomac.8b01473

231. 231.

     Nuhn L, Vanparijs N, Beuckelaer AD, Lybaert L, Verstraete G, Deswarte K, Lienenklaus S, Shukla NM, Salyer ACD, Lambrecht BN, Grooten J, David SA, Koker SD, Geest BGD, pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation, Proceedings of the National Academy of Sciences. 113 (2016 )..

     Not in our library10.1073/pnas.1600816113

232. 232.

     Nuhn L, Hoecke LV, Deswarte K, Schepens B, Li Y, Lambrecht BN, Koker SD, David SA, Saelens X, Geest BGD, Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7/8 agonist, Biomaterials. 178 (2018 ) 643–651..

     Not in our library10.1016/j.biomaterials.2018.03.026

233. 233.

     Vrieze JD, Louage B, Deswarte K, Zhong Z, Coen RD, Herck SV, Nuhn L, Frich CK, Zelikin AN, Lienenklaus S, Sanders NN, Lambrecht BN, David SA, Geest BGD, Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists, Angewandte Chemie Int Ed. 58 (2019 ) 15390–15395..

     Not in our library10.1002/anie.201905687

234. 234.

     Yoo E, Salyer ACD, Brush MJH, Li Y, Trautman KL, Shukla NM, Beuckelaer AD, Lienenklaus S, Deswarte K, Lambrecht BN, Geest BGD, David SA, Hyaluronic Acid Conjugates of TLR7/8 Agonists for Targeted Delivery to Secondary Lymphoid Tissue, Bioconjugate Chem. 29 (2018 ) 2741–2754..

     Not in our library10.1021/acs.bioconjchem.8b00386

235. 235.

     Ilyinskii PO, Roy CJ, O’Neil CP, Browning EA, Pittet LA, Altreuter DH, Alexis F, Tonti E, Shi J, Basto PA, Iannacone M, Radovic-Moreno AF, Langer RS, Farokhzad OC, von Andrian UH, Johnston LPM, Kishimoto TK, Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release, Vaccine. 32 (2014 ) 2882–95..

     Not in our library10.1016/j.vaccine.2014.02.027

236. 236.

     Kim WG, Choi B, Yang H-J, Han J-A, Jung H, Cho H, Kang S, Hong SY, Covalent Conjugation of Small-Molecule Adjuvants to Nanoparticles Induces Robust Cytotoxic T Cell Responses via DC Activation, Bioconjugate Chemistry. 27 (2016 ) 2007–13..

     Not in our library10.1021/acs.bioconjchem.6b00277

237. 237.

     Liong CS, Smith AAA, Mann JL, Roth GA, Gale EC, Maikawa CL, Ou BS, Appel Eric.A., Enhanced Humoral Immune Response by High Density TLR Agonist Presentation on Hyperbranched Polymers, Adv Ther. (2021 ) 2000081..

     Not in our library10.1002/adtp.202000081

238. 238.

     Wu TY-H, Singh M, Miller AT, Gregorio ED, Doro F, D’Oro U, Skibinski DAG, Mbow ML, Bufali S, Herman AE, Cortez A, Li Y, Nayak BP, Tritto E, Filippi CM, Otten GR, Brito LA, Monaci E, Li C, Aprea S, Valentini S, Calabró S, Laera D, Brunelli B, Caproni E, Malyala P, Panchal RG, Warren TK, Bavari S, O’Hagan DT, Cooke MP, Valiante NM, Rational design of small molecules as vaccine adjuvants, Sci Transl Med. 6 (2014 ) 263ra160–263ra160..

     Not in our library10.1126/scitranslmed.3009980

239. 239.

     Buonsanti C, Balocchi C, Harfouche C, Corrente F, Stampino LG, Mancini F, Tontini M, Malyala P, Bufali S, Baudner B, Gregorio ED, Valiante NM, O’Hagan DT, Rappuoli R, D’Oro U, Novel adjuvant Alum-TLR7 significantly potentiates immune response to glycoconjugate vaccines, Sci Rep-Uk. 6 (2016 ) 29063..

     Not in our library10.1038/srep29063

240. 240.

     Bagnoli F, Fontana MR, Soldaini E, Mishra RPN, Fiaschi L, Cartocci E, Nardi-Dei V, Ruggiero P, Nosari S, Falco MGD, Lofano G, Marchi S, Galletti B, Mariotti P, Bacconi M, Torre A, Maccari S, Scarselli M, Rinaudo CD, Inoshima N, Savino S, Mori E, Rossi-Paccani S, Baudner B, Pallaoro M, Swennen E, Petracca R, Brettoni C, Liberatori S, Norais N, Monaci E, Wardenburg JB, Schneewind O, O’Hagan DT, Valiante NM, Bensi G, Bertholet S, Gregorio ED, Rappuoli R, Grandi G, Vaccine composition formulated with a novel TLR7-dependent adjuvant induces high and broad protection against Staphylococcus aureus, P Natl Acad Sci Usa. 112 (2015 ) 3680–5..

     Not in our library10.1073/pnas.1424924112

241. 241.

     Mancini F, Monaci E, Lofano G, Torre A, Bacconi M, Tavarini S, Sammicheli C, Arcidiacono L, Galletti B, Laera D, Pallaoro M, Tuscano G, Fontana MR, Bensi G, Grandi G, Rossi-Paccani S, Nuti S, Rappuoli R, Gregorio ED, Bagnoli F, Soldaini E, Bertholet S, One Dose of Staphylococcus aureus 4C-Staph Vaccine Formulated with a Novel TLR7-Dependent Adjuvant Rapidly Protects Mice through Antibodies, Effector CD4+ T Cells, and IL-17A, Plos One. 11 (2016 ) e0147767..

     Not in our library10.1371/journal.pone.0147767

242. 242.

     Misiak A, Leuzzi R, Allen AC, Galletti B, Baudner BC, D’Oro U, O’Hagan DT, Pizza M, Seubert A, Mills KHG, Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model, Vaccine. 35 (2017 ) 5256–5263..

     Not in our library10.1016/j.vaccine.2017.08.009

243. 243.

     Malyala P, Laera D, Cianetti S, Bufali S, Aggravi M, Ianni E, Judge C, Otten G, Singh M, Hagan DTO, The preparation and physico-chemical characterization of aluminum hydroxide/TLR7a, a novel vaccine adjuvant comprising a small molecule adsorbed to aluminum hydroxide, J Pharm Sci. 107 (2018 ) 1577–1585..

     Not in our library10.1016/j.xphs.2018.01.024

244. 244.

     Gonzalez-Lopez A, Oostendorp J, Koernicke T, Fadini T, D’Oro U, Baker S, O’Hagan DT, Giudice GD, Siena E, Finco O, Medini D, Adjuvant effect of TLR7 agonist adsorbed on aluminum hydroxide (AS37): A phase I randomized, dose escalation study of an AS37-adjuvanted meningococcal C conjugated vaccine, Clin Immunol. 209 (2019 ) 108275..

     Not in our library10.1016/j.clim.2019.108275

245. 245.

     Fox CB, Orr MT, Hoeven NV, Parker SC, Mikasa TJT, Phan T, Beebe EA, Nana GI, Joshi SW, Tomai MA, Elvecrog J, Fouts TR, Reed SG, Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach, J Control Release. 244 (2016 ) 98–107..

     Not in our library10.1016/j.jconrel.2016.11.011

246. 246.

     Francica JR, Zak DE, Linde C, Siena E, Johnson C, Juraska M, Yates NL, Gunn B, Gregorio ED, Flynn BJ, Valiante NM, Malyala P, Barnett SW, Sarkar P, Singh M, Jain S, Ackerman M, Alam M, Ferrari G, Tomaras GD, O’Hagan DT, Aderem A, Alter G, Seder RA, Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs, Blood Adv. 1 (2017 ) 2329–2342..

     Not in our library10.1182/bloodadvances.2017011411

247. 247.

     Vaccari M, Gordon S, Fourati S, Schifanella L, Liyanage N, Cameron M, Keele B, Shen X, Tomaras G, Billings E, Rao M, Chung A, Dowell K, Bailey-Kellogg C, Brown E, Ackerman M, Vargas-Inchaustegui D, Whitney S, Doster M, Binello N, Pegu P, Montefiori D, Foulds K, Quinn D, Donaldson M, Liang F, Loré K, Roederer M, Koup R, McDermott A, Ma Z, Miller C, Phan T, Forthal D, Blackburn M, Caccuri F, Bissa M, Ferrari G, Kalyanaraman V, Ferrari M, Thompson D, Robert-Guroff M, Ratto-Kim S, Kim J, Michael N, Phogat S, Barnett S, Tartaglia J, Venzon D, Stablein D, Alter G, Sekaly R, Franchini G, Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition, Nat Med. 22 (2016 ) 762–770..

     Not in our library10.1038/nm.4105

248. 248.

     Singh M, Ugozzoli M, Kazzaz J, Chesko J, Soenawan E, Mannucci D, Titta F, Contorni M, Volpini G, Guidice G, O’Hagan D, A preliminary evaluation of alternative adjuvants to alum using a range of established and new generation vaccine antigens, Vaccine. 24 (2006 ) 1680–1686..

     Not in our library10.1016/j.vaccine.2005.09.046

249. 249.
     Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques · 2021

     Not checked
250. 250.

     Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V, Ganneru B, Sapkal G, Yadav P, Abraham P, Panda S, Gupta N, Reddy P, Verma S, Rai SK, Singh C, Redkar SV, Gillurkar CS, Kushwaha JS, Mohapatra S, Rao V, Guleria R, Ella K, Bhargava B, Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial, Lancet Infect Dis. (2021 )..

     Not in our library10.1016/s1473-3099(20)30942-7

251. 251.

     Ganneru B, Jogdand H, Daram VK, Das D, Molugu NR, Prasad SD, Kannappa SV, Ella KM, Ravikrishnan R, Awasthi A, Jose J, Rao P, Kumar D, Ella R, Abraham P, Yadav PD, Sapkal GN, Shete-Aich A, Desphande G, Mohandas S, Basu A, Gupta N, Vadrevu KM, Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation, Iscience. 24 (2021 ) 102298..

     Not in our library10.1016/j.isci.2021.102298

252. 252.

     Ella R, Reddy S, Jogdand H, Sarangi V, Ganneru B, Prasad S, Das D, Raju D, Praturi U, Sapkal G, Yadav P, Reddy P, Verma S, Singh C, Redkar SV, Gillurkar CS, Kushwaha JS, Mohapatra S, Bhate A, Rai S, Panda S, Abraham P, Gupta N, Ella K, Bhargava B, Vadrevu KM, Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial, Lancet Infect Dis. (2021 )..

     Not in our library10.1016/s1473-3099(21)00070-0

253. 253.

     Li J-X, Zhu F-C, Adjuvantation helps to optimise COVID-19 vaccine candidate, Lancet Infect Dis. (2021 )..

     Not in our library10.1016/s1473-3099(21)00094-3

254. 254.

     Jangra S, Vrieze JD, Choi A, Rathnasinghe R, Laghlali G, Uvyn A, Herck SV, Nuhn L, Deswarte K, Zhong Z, Sanders N, Lienenklaus S, David S, Strohmeier S, Amanat F, Krammer F, Hammad H, Lambrecht BN, Coughlan L, García-Sastre A, de Geest B, Schotsaert M, Sterilizing Immunity against SARS-CoV-2 Infection in Mice by a Single-Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist-Adjuvanted Recombinant Spike Protein Vaccine, Angewandte Chemie Int Ed. (2021 )..

     Not in our library10.1002/anie.202015362

255. 255.

     Petitdemange C, Kasturi SP, Kozlowski PA, Nabi R, Quarnstrom CF, Reddy PBJ, Derdeyn CA, Spicer LM, Patel P, Legere T, Kovalenkov YO, Labranche CC, Villinger F, Tomai M, Vasilakos J, Haynes B, Kang CY, Gibbs JS, Yewdell JW, Barouch D, Wrammert J, Montefiori D, Hunter E, Amara RR, Masopust D, Pulendran B, Vaccine induction of antibodies and tissue-resident CD8+ T cells enhances protection against mucosal SHIV-infection in young macaques, Jci Insight. 4 (2019 ) e126047..

     Not in our library10.1172/jci.insight.126047

256. 256.
     T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers · 2020

     No notice
257. 257.

     Philbin VJ, Dowling DJ, Gallington LC, Cortés G, Tan Z, Suter EE, Chi KW, Shuckett A, Stoler-Barak L, Tomai M, Miller RL, Mansfield K, Levy O, Imidazoquinoline Toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1-dependent pathways., J Allergy Clin Immunol. 130 (2012 ) 195–204.e9..

     Not in our library10.1016/j.jaci.2012.02.042

258. 258.

     Primard C, Poecheim J, Heuking S, Sublet E, Esmaeili F, Borchard G, Multifunctional PLGA-Based Nanoparticles Encapsulating Simultaneously Hydrophilic Antigen and Hydrophobic Immunomodulator for Mucosal Immunization, Mol Pharmaceut. 10 (2013 ) 2996–3004..

     Not in our library10.1021/mp400092y

259. 259.

     Kim H, Niu L, Larson P, Kucaba TA, Murphy KA, James BR, Ferguson DM, Griffith TS, Panyam J, Polymeric nanoparticles encapsulating novel TLR7/8 agonists as immunostimulatory adjuvants for enhanced cancer immunotherapy, Biomaterials. 164 (2018 ) 38–53..

     Not in our library10.1016/j.biomaterials.2018.02.034

260. 260.

     Sevimli S, Knight FC, Gilchuk P, Joyce S, Wilson JT, Fatty Acid-Mimetic Micelles for Dual Delivery of Antigens and Imidazoquinoline Adjuvants, Acs Biomater Sci Eng. 3 (2017 ) 179–194..

     Not in our library10.1021/acsbiomaterials.6b00408

261. 261.
     Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses · 2017

     No notice
262. 262.

     Vicente S, Peleteiro M, Díaz-Freitas B, Sanchez A, González-Fernández Á, Alonso MJ, Co-delivery of viral proteins and a TLR7 agonist from polysaccharide nanocapsules: A needle-free vaccination strategy, J Control Release. 172 (2013 ) 773–781..

     Not in our library10.1016/j.jconrel.2013.09.012

263. 263.

     Kim NW, Kim S-Y, Lee JE, Yin Y, Lee JH, Lim SY, Kim ES, Duong HTT, Kim HK, Kim S, Kim J-E, Lee DS, Kim J, Lee MS, Lim YT, Jeong JH, Enhanced Cancer Vaccination by In Situ Nanomicelle-Generating Dissolving Microneedles, Acs Nano. 12 (2018 ) 9702–9713..

     Not in our library10.1021/acsnano.8b04146

264. 264.

     Park W, Seong KY, Han HH, Yang SY, Hahn SK, Dissolving microneedles delivering cancer cell membrane coated nanoparticles for cancer immunotherapy, Rsc Adv. 11 (2021 ) 10393–10399..

     Not in our library10.1039/d1ra00747e

265. 265.

     Chan M, Hayashi T, Mathewson RD, Yao S, Gray C, Tawatao RI, Kalenian K, Zhang Y, Hayashi Y, Lao FS, Cottam HB, Carson DA, Synthesis and Characterization of PEGylated Toll Like Receptor 7 Ligands, Bioconjugate Chem. 22 (2011 ) 445–454..

     Not in our library10.1021/bc1004813

266. 266.

     Ryu KA, Slowinska K, Moore T, Esser-Kahn A, Immune Response Modulation of Conjugated Agonists with Changing Linker Length, Acs Chem Biol. 11 (2016 ) 3347–3352..

     Not in our library10.1021/acschembio.6b00895

267. 267.

     Wu CCN, Hayashi T, Takabayashi K, Sabet M, Smee DF, Guiney DD, Cottam HB, Carson DA, Immunotherapeutic activity of a conjugate of a Toll-like receptor 7 ligand, Proc National Acad Sci. 104 (2007 ) 3990–3995..

     Not in our library10.1073/pnas.0611624104

268. 268.

     Shinchi H, Crain B, Yao S, Chan M, Zhang SS, Ahmadiiveli A, Suda Y, Hayashi T, Cottam HB, Carson DA, Enhancement of the Immunostimulatory Activity of a TLR7 Ligand by Conjugation to Polysaccharides, Bioconjugate Chemistry. 26 (2015 ) 1713–23..

     Not in our library10.1021/acs.bioconjchem.5b00285

269. 269.

     Hosoya T, Sato-Kaneko F, Ahmadi A, Yao S, Lao F, Kitaura K, Matsutani T, Carson DA, Hayashi T, Induction of oligoclonal CD8 T cell responses against pulmonary metastatic cancer by a phospholipid-conjugated TLR7 agonist, Proc National Acad Sci. 115 (2018 ) 201803281..

     Not in our library10.1073/pnas.1803281115

270. 270.

     Duong AD, Sharma S, Peine KJ, Gupta G, Satoskar AR, Bachelder EM, Wyslouzil BE, Ainslie KM, Electrospray Encapsulation of Toll-Like Receptor Agonist Resiquimod in Polymer Microparticles for the Treatment of Visceral Leishmaniasis, Mol Pharmaceut. 10 (2013 ) 1045–1055..

     Not in our library10.1021/mp3005098

271. 271.

     Rodell CB, Arlauckas SP, Cuccarese MF, Garris CS, Li R, Ahmed MS, Kohler RH, Pittet MJ, Weissleder R, TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy, Nature Biomedical Engineering. 2 (2018 ) 578–588..

     Not in our library10.1038/s41551-018-0236-8

272. 272.

     Rodell CB, Ahmed MS, Garris CS, Pittet MJ, Weissleder R, Development of Adamantane-Conjugated TLR7/8 Agonists for Supramolecular Delivery and Cancer Immunotherapy, Theranostics. 9 (2019 ) 8426–8436..

     Not in our library10.7150/thno.35434

273. 273.

     Koch PD, Rodell CB, Kohler RH, Pittet MJ, Weissleder R, Myeloid Cell-Targeted Nanocarriers Efficiently Inhibit Cellular Inhibitor of Apoptosis for Cancer Immunotherapy, Cell Chem Biol. 27 (2020 )..

     Not in our library10.1016/j.chembiol.2019.12.007

274. 274.

     Vinod N, Hwang D, Azam S, Swearingen A, Wayne E, Fussell S, Sokolsky-Papkov M, Pecot C, Kabanov A, High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma., Sci Adv. 6 (2020 ) eaba5542..

     Not in our library10.1126/sciadv.aba5542

275. 275.

     Mottas I, Bekdemir A, Cereghetti A, Spagnuolo L, Yang Y-SS, Müller M, Irvine DJ, Stellacci F, Bourquin C, Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation, Biomaterials. 190 (2019 ) 111–120..

     Not in our library10.1016/j.biomaterials.2018.10.031

276. 276.

     Scott EA, Stano A, Gillard M, Maio-Liu AC, Swartz MA, Hubbell JA, Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes, Biomaterials. 33 (2012 ) 6211–6219..

     Not in our library10.1016/j.biomaterials.2012.04.060

277. 277.

     Manaster AJ, Batty C, Tiet P, Ooi A, Bachelder EM, Ainslie KM, Broaders KE, Oxidation-Sensitive Dextran-Based Polymer with Improved Processability through Stable Boronic Ester Groups, Acs Appl Bio Mater. 2 (2019 ) 3755–3762..

     Not in our library10.1021/acsabm.9b00399

278. 278.

     Ryu KA, Stutts L, Tom JK, Mancini RJ, Esser-Kahn AP, Stimulation of Innate Immune Cells by Light-Activated TLR7/8 Agonists, J Am Chem Soc. 136 (2014 ) 10823–10825..

     Not in our library10.1021/ja412314j

279. 279.

     Hantho JD, Strayer TA, Nielsen AE, Mancini RJ, An Enzyme-Directed Imidazoquinoline for Cancer Immunotherapy, ChemMedChem. 11 (2016 ) 2496–2500..

     Not in our library10.1002/cmdc.201600443

280. 280.

     Ryan AT, Pulukuri AJ, Davaritouchaee M, Abbasi A, Hendricksen AT, Opp LK, Burt AJ, Nielsen AE, Mancini RJ, Comparing the immunogenicity of glycosidase-directed resiquimod prodrugs mediated by cancer cell metabolism, Acta Pharmacol Sin. 41 (2020 ) 995–1004..

     Not in our library10.1038/s41401-020-0432-4

281. 281.

     Wang B, Herck SV, Chen Y, Bai X, Zhong Z, Deswarte K, Lambrecht BN, Sanders NN, Lienenklaus S, Scheeren HW, David SA, Kiessling F, Lammers T, Geest BGD, Shi Y, Potent and Prolonged Innate Immune Activation by Enzyme-Responsive Imidazoquinoline TLR7/8 Agonist Prodrug Vesicles, J Am Chem Soc. (2020 )..

     Not in our library10.1021/jacs.0c01928

282. 282.
     T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity · 2017

     No notice
283. 283.

     Tacken PJ, Zeelenberg IS, Cruz LJ, van Hout-Kuijer MA, van de Glind G, Fokkink RG, Lambeck AJA, Figdor CG, Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity, Blood. 118 (2011 ) 6836–6844..

     Not in our library10.1182/blood-2011-07-367615

284. 284.

     Gadd AJR, Greco F, Cobb AJA, Edwards AD, Targeted Activation of Toll-Like Receptors: Conjugation of a Toll-Like Receptor 7 Agonist to a Monoclonal Antibody Maintains Antigen Binding and Specificity, Bioconjugate Chem. 26 (2015 ) 1743–1752..

     Not in our library10.1021/acs.bioconjchem.5b00302

285. 285.

     Klauber TCB, Laursen JM, Zucker D, Brix S, Jensen SS, Andresen TL, Delivery of TLR7 agonist to monocytes and dendritic cells by DCIR targeted liposomes induces robust production of anti-cancer cytokines, Acta Biomater. 53 (2017 ) 367–377..

     Not in our library10.1016/j.actbio.2017.01.072

286. 286.

     Johansen PT, Zucker D, Parhamifar L, Pourhassan H, Madsen DV, Henriksen JR, Gad M, Barberis A, Maj R, Andresen TL, Jensen SS, Monocyte targeting and activation by cationic liposomes formulated with a TLR7 agonist, Expert Opin Drug Del. 12 (2015 ) 1045–58..

     Not in our library10.1517/17425247.2015.1009444

287. 287.

     Miller JB, Zhang S, Kos P, Xiong H, Zhou K, Perelman SS, Zhu H, Siegwart DJ, Non-Viral CRISPR/Cas Gene Editing In Vitro and In Vivo Enabled by Synthetic Nanoparticle Co-Delivery of Cas9 mRNA and sgRNA., Angewandte Chemie Int Ed Engl. 56 (2016 ) 1059–1063..

     Not in our library10.1002/anie.201610209

288. 288.

     Cheng Q, Wei T, Farbiak L, Johnson LT, Dilliard SA, Siegwart DJ, Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing, Nat Nanotechnol. 15 (2020 ) 313–320..

     Not in our library10.1038/s41565-020-0669-6

289. 289.

     Aznar MA, Tinari N, Rullán AJ, Sánchez-Paulete AR, Rodriguez-Ruiz ME, Melero I, Intratumoral Delivery of Immunotherapy—Act Locally, Think Globally, J Immunol. 198 (2017 ) 31–39..

     Not in our library10.4049/jimmunol.1601145

290. 290.

     Sloot S, Rashid OM, Zager JS, Intralesional therapy for metastatic melanoma, Expert Opin Pharmaco. 15 (2014 ) 2629–2639..

     Not in our library10.1517/14656566.2014.967682

291. 291.
     Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy · 2016

     No notice
292. 292.

     Hammerich L, Marron TU, Upadhyay R, Svensson-Arvelund J, Dhainaut M, Hussein S, Zhan Y, Ostrowski D, Yellin M, Marsh H, Salazar AM, Rahman AH, Brown BD, Merad M, Brody JD, Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination, Nature Medicine. 25 (2019 ) 814–824..

     Not in our library10.1038/s41591-019-0410-x

293. 293.

     Daud A, Algazi AP, Ashworth MT, Fong L, Lewis J, Chan SE, Buljan M, Molina MA, Takamura KT, Diep TT, Heller R, Pierce RH, Bhatia S, Systemic antitumor effect and clinical response in a phase 2 trial of intratumoral electroporation of plasmid interleukin-12 in patients with advanced melanoma., J Clin Oncol. 32 (2014 ) 9025–9025..

     Not in our library10.1200/jco.2014.32.15_suppl.9025

294. 294.

     Hong WX, Haebe S, Lee AS, Westphalen CB, Norton JA, Jiang W, Levy R, Intratumoral Immunotherapy for Early-stage Solid Tumors, Clin Cancer Res. (2020 ) clincanres.3642.2019..

     Not in our library10.1158/1078-0432.ccr-19-3642

295. 295.

     Gupta S, Grilley-Olson J, Hong D, Marabelle A, Munster P, Aggarwal R, Aspeslagh S, Dixon RG, Patel M, Subbiah V, Morehouse C, Wu Y, Zha J, Tseng L, Cooper ZA, Morris S, Brody J, Abstract CT091: Safety and pharmacodynamic activity of MEDI9197, a TLR 7/8 agonist, administered intratumorally in subjects with solid tumors, (2017 ) CT091–CT091..

     Not in our library10.1158/1538-7445.am2017-ct091

296. 296.

     Fakhari A, Nugent S, Elvecrog J, Vasilakos J, Corcoran M, Tilahun A, Siebenaler K, Sun J, Subramony JA, Schwarz A, Thermosensitive Gel–Based Formulation for Intratumoral Delivery of Toll-Like Receptor 7/8 Dual Agonist, MEDI9197, J Pharm Sci. 106 (2017 ) 2037–2045..

     Not in our library10.1016/j.xphs.2017.04.041

297. 297.

     Smirnov D, Schmidt JJ, Capecchi JT, Wightman PD, Vaccine adjuvant activity of 3M-052: An imidazoquinoline designed for local activity without systemic cytokine induction, Vaccine. 29 (2011 ) 5434–5442..

     Not in our library10.1016/j.vaccine.2011.05.061

298. 298.

     Cortez A, Li Y, Miller AT, Zhang X, Yue K, Maginnis J, Hampton J, Hall DS, Shapiro M, Nayak B, D’Oro U, Li C, Skibinski D, Mbow ML, Singh M, O’Hagan DT, Cooke MP, Valiante NM, Wu TY-H, Incorporation of Phosphonate into Benzonaphthyridine Toll-like Receptor 7 Agonists for Adsorption to Aluminum Hydroxide, J Med Chem. 59 (2016 ) 5868–5878..

     Not in our library10.1021/acs.jmedchem.6b00489

299. 299.

     Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies, https://clinicaltrials.gov/ct2/show/NCT03301896.

     Not in our library

300. 300.

     Georges B, Immunogenic Compound, US10,434,183 B2, 2019. https://patentimages.storage.googleapis.com/72/16/72/6d37b4c964d73a/US10434183.pdf.

     Not in our library

301. 301.
     34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2 · 2019

     Not checked
302. 302.

     Nuhn L, Koker SD, Lint SV, Zhong Z, Catani JP, Combes F, Deswarte K, Li Y, Lambrecht BN, Lienenklaus S, Sanders NN, David SA, Tavernier J, Geest BGD, Nanoparticle-Conjugate TLR7/8 Agonist Localized Immunotherapy Provokes Safe Antitumoral Responses, Adv Mater. 30 (2018 ) 1803397..

     Not in our library10.1002/adma.201803397

303. 303.

     Kim S-Y, Kim S, Kim J-E, Lee SN, Shin IW, Shin HS, Jin SM, Noh Y-W, Kang YJ, Kim YS, Kang TH, Park Y-M, Lim YT, Lyophilizable and Multifaceted Toll-like Receptor 7/8 Agonist-Loaded Nanoemulsion for the Reprogramming of Tumor Microenvironments and Enhanced Cancer Immunotherapy, Acs Nano. 13 (2019 ) 12671–12686..

     Not in our library10.1021/acsnano.9b04207

304. 304.

     Lu R, Groer C, Kleindl PA, Moulder KR, Huang A, Hunt JR, Cai S, Aires DJ, Berkland C, Forrest L, Formulation and preclinical evaluation of a toll-like receptor 7/8 agonist as an anti-tumoral immunomodulator, Journal of Controlled Release. 306 (2019 ) 165–176..

     Not in our library10.1016/j.jconrel.2019.06.003

305. 305.

     Vohidov F, Milling LE, Chen Q, Zhang W, Bhagchandani S, Nguyen HV-T, Irvine DJ, Johnson JA, ABC triblock bottlebrush copolymer-based injectable hydrogels: design, synthesis, and application to expanding the therapeutic index of cancer immunochemotherapy, Chem Sci. (2020 )..

     Not in our library10.1039/d0sc02611e

306. 306.

     Kockelmann J, Stickdorn J, Kasmi S, Vrieze JD, Pieszka M, Ng DYW, David SA, Geest BGD, Nuhn L, Control over Imidazoquinoline Immune Stimulation by pH-Degradable Poly(norbornene) Nanogels, Biomacromolecules. 21 (2020 )..

     Not in our library10.1021/acs.biomac.0c00205

307. 307.
     Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors · 2021

     No notice
308. 308.

     Park CG, Hartl CA, Schmid D, Carmona EM, Kim H-J, Goldberg MS, Extended release of perioperative immunotherapy prevents tumor recurrence and eliminates metastases, Sci Transl Med. 10 (2018 ) eaar1916..

     Not in our library10.1126/scitranslmed.aar1916

309. 309.

     Melero I, Berman D, Aznar M, Korman A, Gracia J, Haanen J, Evolving synergistic combinations of targeted immunotherapies to combat cancer, Nat Rev Cancer. 15 (2015 ) 457–472..

     Not in our library10.1038/nrc3973

310. 310.

     Lo JA, Kawakubo M, Juneja VR, Su MY, Erlich TH, LaFleur MW, Kemeny LV, Rashid M, Malehmir M, Rabi SA, Raghavan R, Allouche J, Kasumova G, Frederick DT, Pauken KE, Weng QY, da Silva MP, Xu Y, van der Sande AAJ, Silkworth W, Roider E, Browne EP, Lieb DJ, Wang B, Garraway LA, Wu CJ, Flaherty KT, Brinckerhoff CE, Mullins DW, Adams DJ, Hacohen N, Hoang MP, Boland GM, Freeman GJ, Sharpe AH, Manstein D, Fisher DE, Epitope spreading toward wild-type melanocyte-lineage antigens rescues suboptimal immune checkpoint blockade responses, Sci Transl Med. 13 (2021 ) eabd8636..

     Not in our library10.1126/scitranslmed.abd8636

311. 311.

     Wang L, Gao Y, Zhang G, Li D, Wang Z, Zhang J, Hermida LC, He L, Wang Z, Si J, Geng S, Ai R, Ning F, Cheng C, Deng H, Dimitrov DS, Sun Y, Huang Y, Wang D, Hu X, Wei Z, Wang W, Liao X, Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade, Sci Transl Med. 12 (2020 ) eaax2282..

     Not in our library10.1126/scitranslmed.aax2282

312. 312.

     Querec T, Bennouna S, Alkan S, Laouar Y, Gorden K, Flavell R, Akira S, Ahmed R, Pulendran B, Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity, J Exp Medicine. 203 (2006 ) 413–424..

     Not in our library10.1084/jem.20051720

313. 313.

     Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A, Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1–polarizing program in dendritic cells, Nat Immunol. 6 (2005 ) 769–776..

     Not in our library10.1038/ni1223

314. 314.

     Maisonneuve C, Bertholet S, Philpott DJ, Gregorio ED, Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants, Proceedings of the National Academy of Sciences. 111 (2014 )..

     Not in our library10.1073/pnas.1400478111

315. 315.

     Shekarian T, Valsesia-Wittmann S, Brody J, Michallet MC, Depil S, Caux C, Marabelle A, Pattern recognition receptors: immune targets to enhance cancer immunotherapy, (2017 )..

     Not in our library10.1093/annonc/mdx179

316. 316.

     Kasturi SP, Skountzou I, Albrecht RA, Koutsonanos D, Hua T, Nakaya HI, Ravindran R, Stewart S, Alam M, Kwissa M, Villinger F, Murthy N, Steel J, Jacob J, Hogan RJ, García-Sastre A, Compans R, Pulendran B, Programming the magnitude and persistence of antibody responses with innate immunity, Nature. 470 (2011 ) 543..

     Not in our library10.1038/nature09737

317. 317.

     Kasturi SP, Kozlowski PA, Nakaya HI, Burger MC, Russo P, Pham M, Kovalenkov Y, Silveira ELV, Havenar-Daughton C, Burton SL, Kilgore KM, Johnson MJ, Nabi R, Legere T, Sher ZJ, Chen X, Amara RR, Hunter E, Bosinger SE, Spearman P, Crotty S, Villinger F, Derdeyn CA, Wrammert J, Pulendran B, Adjuvanting a Simian Immunodeficiency Virus Vaccine with Toll-Like Receptor Ligands Encapsulated in Nanoparticles Induces Persistent Antibody Responses and Enhanced Protection in TRIM5α Restrictive Macaques, J Virol. 91 (2017 ) e01844–16..

     Not in our library10.1128/jvi.01844-16

318. 318.

     Kasturi SP, Rasheed MAU, Havenar-Daughton C, Pham M, Legere T, Sher ZJ, Kovalenkov Y, Gumber S, Huang JY, Gottardo R, Fulp W, Sato A, Sawant S, Stanfield-Oakley S, Yates N, LaBranche C, Alam SM, Tomaras G, Ferrari G, Montefiori D, Wrammert J, Villinger F, Tomai M, Vasilakos J, Fox CB, Reed SG, Haynes BF, Crotty S, Ahmed R, Pulendran B, 3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope–specific plasma cells and humoral immunity in nonhuman primates, Sci Immunol. 5 (2020 ) eabb1025..

     Not in our library10.1126/sciimmunol.abb1025

319. 319.

     Fox CB, Sivananthan SJ, Duthie MS, Vergara J, Guderian JA, Moon E, Coblentz D, Reed SG, Carter D, A nanoliposome delivery system to synergistically trigger TLR4 AND TLR7, J Nanobiotechnol. 12 (2014 ) 17..

     Not in our library10.1186/1477-3155-12-17

320. 320.

     Rizwan SB, McBurney WT, Young K, Hanley T, Boyd BJ, Rades T, Hook S, Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate robust cellular and humoral immune responses, J Control Release. 165 (2013 ) 16–21..

     Not in our library10.1016/j.jconrel.2012.10.020

321. 321.

     Goff PH, Hayashi T, Martínez-Gil L, Corr M, Crain B, Yao S, Cottam HB, Chan M, Ramos I, Eggink D, Heshmati M, Krammer F, Messer K, Pu M, Fernandez-Sesma A, Palese P, Carson DA, Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands as Influenza Virus Vaccine Adjuvants Induce Rapid, Sustained, and Broadly Protective Responses, Journal of Virology. 89 (2015 )..

     Not in our library10.1128/jvi.03337-14

322. 322.

     McKay PF, King DFL, Mann JFS, Barinaga G, Carter D, Shattock RJ, TLR4 and TLR7/8 Adjuvant Combinations Generate Different Vaccine Antigen-Specific Immune Outcomes in Minipigs when Administered via the ID or IN Routes, Plos One. 11 (2016 ) e0148984..

     Not in our library10.1371/journal.pone.0148984

323. 323.

     Moody MA, Santra S, Vandergrift NA, Sutherland LL, Gurley TC, Drinker MS, Allen AA, Xia S-M, Meyerhoff RR, Parks R, Lloyd KE, Easterhoff D, Alam SM, Liao H-X, Ward BM, Ferrari G, Montefiori DC, Tomaras GD, Seder RA, Letvin NL, Haynes BF, Toll-Like Receptor 7/8 (TLR7/8) and TLR9 Agonists Cooperate To Enhance HIV-1 Envelope Antibody Responses in Rhesus Macaques, J Virol. 88 (2014 ) 3329–3339..

     Not in our library10.1128/jvi.03309-13

324. 324.

     Madan-Lala R, Pradhan P, Roy K, Combinatorial Delivery of Dual and Triple TLR Agonists via Polymeric Pathogen-like Particles Synergistically Enhances Innate and Adaptive Immune Responses, Scientific Reports. 7 (2017 ) 2530..

     Not in our library10.1038/s41598-017-02804-y

325. 325.

     Tom JK, Dotsey EY, Wong HY, Stutts L, Moore T, Davies DH, Felgner PL, Esser-Kahn AP, Modulation of Innate Immune Responses via Covalently Linked TLR Agonists, Acs Central Sci. 1 (2015 ) 439–448..

     Not in our library10.1021/acscentsci.5b00274

326. 326.

     Kimani FW, Ajit J, Galluppi A, Manna S, Howitz WJ, Tang S, Esser-Kahn AP, Receptor–Ligand Kinetics Influence the Mechanism of Action of Covalently Linked TLR Ligands, Acs Chem Biol. (2021 )..

     Not in our library10.1021/acschembio.0c00924

327. 327.

     Bagchi A, Herrup EA, Warren HS, Trigilio J, Shin H-S, Valentine C, Hellman J, MyD88-Dependent and MyD88-Independent Pathways in Synergy, Priming, and Tolerance between TLR Agonists, J Immunol. 178 (2007 ) 1164–1171..

     Not in our library10.4049/jimmunol.178.2.1164

328. 328.

     Whitmore MM, DeVeer MJ, Edling A, Oates RK, Simons B, Lindner D, Williams BRG, Synergistic Activation of Innate Immunity by Double-Stranded RNA and CpG DNA Promotes Enhanced Antitumor Activity, Cancer Res. 64 (2004 ) 5850–5860..

     Not in our library10.1158/0008-5472.can-04-0063

329. 329.

     Albin TJ, Tom JK, Manna S, Gilkes AP, Stetkevich SA, Katz BB, Supnet M, Felgner J, Jain A, Nakajima R, Jasinskas A, Zlotnik A, Pearlman E, Davies DH, Felgner PL, Burkhardt AM, Esser-Kahn AP, Linked Toll-Like Receptor Triagonists Stimulate Distinct, Combination-Dependent Innate Immune Responses, Acs Central Sci. 5 (2019 ) 1137–1145..

     Not in our library10.1021/acscentsci.8b00823

330. 330.

     Manna S, Maiti S, Shen J, Du W, Esser-Kahn AP, Pathogen-like Nanoassemblies of Covalently Linked TLR Agonists Enhance CD8 and NK Cell-Mediated Antitumor Immunity, Acs Central Sci. 6 (2020 ) 2071–2078..

     Not in our library10.1021/acscentsci.0c01001

331. 331.

     Pradhan P, Toy R, Jhita N, Atalis A, Pandey B, Beach A, Blanchard EL, Moore SG, Gaul DA, Santangelo PJ, Shayakhmetov DM, Roy K, TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation, Sci Adv. 7 (2021 ) eabd4235..

     Not in our library10.1126/sciadv.abd4235

332. 332.

     Ni Q, Zhang F, Liu Y, Wang Z, Yu G, Liang B, Niu G, Su T, Zhu G, Lu G, Zhang L, Chen X, A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer, Sci Adv. 6 (2020 ) eaaw6071..

     Not in our library10.1126/sciadv.aaw6071

333. 333.

     Toy R, Keenum MC, Pradhan P, Phang K, Chen P, Chukwu C, Nguyen LAH, Liu J, Jain S, Kozlowski G, Hosten J, Suthar MS, Roy K, TLR7 and RIG-I dual-adjuvant loaded nanoparticles drive broadened and synergistic responses in dendritic cells in vitro and generate unique cellular immune responses in influenza vaccination, J Control Release. 330 (2021 ) 866–877..

     Not in our library10.1016/j.jconrel.2020.10.060

334. 334.

     Dovedi SJ, Melis MHM, Wilkinson RW, Adlard AL, Stratford IJ, Honeychurch J, Illidge TM, Systemic delivery of a TLR7 agonist in combination with radiation primes durable antitumor immune responses in mouse models of lymphoma, Blood. 121 (2013 ) 251–259..

     Not in our library10.1182/blood-2012-05-432393

335. 335.

     Sagiv-Barfi I, Czerwinski DK, Levy S, Alam IS, Mayer AT, Gambhir SS, Levy R, Eradication of spontaneous malignancy by local immunotherapy, Science Translational Medicine. 10 (2018 ) eaan4488..

     Not in our library10.1126/scitranslmed.aan4488

336. 336.

     Huang C, Mendez N, Echeagaray OH, Weeks J, Wang J, Yao S, Blair SL, Gude N, Trogler WC, Carson DA, Hayashi T, Kummel AC, Immunostimulatory TLR7 Agonist-Nanoparticles Together with Checkpoint Blockade for Effective Cancer Immunotherapy, Adv Ther. 3 (2020 ) 1900200..

     Not in our library10.1002/adtp.201900200

337. 337.

     Sato-Kaneko F, Yao S, Ahmadi A, Zhang SS, Hosoya T, Kaneda MM, Varner JA, Pu M, Messer KS, Guiducci C, Coffman RL, Kitaura K, Matsutani T, Suzuki R, Carson DA, Hayashi T, Cohen EEW, Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer, JCI Insight. 2 (2017 )..

     Not in our library10.1172/jci.insight.93397

338. 338.

     Nishii N, Tachinami H, Kondo Y, Xia Y, Kashima Y, Ohno T, Nagai S, Li L, Lau W, Harada H, Azuma M, Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy, Oncotarget. 9 (2018 ) 13301–13312..

     Not in our library10.18632/oncotarget.24327

339. 339.

     Smith AAA, Gale EC, Roth GA, Maikawa CL, Correa S, Yu AC, Appel EA, Nanoparticles Presenting Potent TLR7/8 Agonists Enhance Anti-PD-L1 Immunotherapy in Cancer Treatment, Biomacromolecules. 21 (2020 ) 3704–3712..

     Not in our library10.1021/acs.biomac.0c00812

340. 340.

     Kim H, Khanna V, Kucaba TA, Zhang W, Sehgal D, Ferguson DM, Griffith TS, Panyam J, TLR7/8 Agonist-Loaded Nanoparticles Augment NK Cell-Mediated Antibody-Based Cancer Immunotherapy, Mol Pharmaceut. 17 (2020 )..

     Not in our library10.1021/acs.molpharmaceut.0c00271

341. 341.

     Hayashi T, Chan M, Norton JT, Wu CCN, Yao S, Cottam HB, Tawatao RI, Corr M, Carson DA, Daniels GA, Additive melanoma suppression with intralesional phospholipid-conjugated TLR7 agonists and systemic IL-2, Melanoma Res. 21 (2011 ) 66–75..

     Not in our library10.1097/cmr.0b013e328340ce6c

342. 342.

     Heo MB, Lim YT, Programmed nanoparticles for combined immunomodulation, antigen presentation and tracking of immunotherapeutic cells, Biomaterials. 35 (2014 ) 590–600..

     Not in our library10.1016/j.biomaterials.2013.10.009

343. 343.

     Silva CGD, Camps MGM, Li TMWY, Chan AB, Ossendorp F, Cruz LJ, Co-delivery of immunomodulators in biodegradable nanoparticles improves therapeutic efficacy of cancer vaccines, Biomaterials. 220 (2019 ) 119417..

     Not in our library10.1016/j.biomaterials.2019.119417

344. 344.

     Khanna V, Kim H, Zhang W, Larson P, Shah M, Griffith TS, Ferguson D, Panyam J, Novel TLR 7/8 agonists for improving NK cell mediated antibody-dependent cellular cytotoxicity (ADCC), Sci Rep-Uk. 11 (2021 ) 3346..

     Not in our library10.1038/s41598-021-83005-6

345. 345.

     Díaz-Carballo D, Saka S, Acikelli AH, Homp E, Erwes J, Demmig R, Klein J, Schröer K, Malak S, D’Souza F, Noa-Bolaño A, Menze S, Pano E, Andrioff S, Teipel M, Dammann P, Klein D, Nasreen A, Tannapfel A, Grandi N, Tramontano E, Ochsenfarth C, Strumberg D, Enhanced antitumoral activity of TLR7 agonists via activation of human endogenous retroviruses by HDAC inhibitors, Commun Biology. 4 (2021 ) 276..

     Not in our library10.1038/s42003-021-01800-3

346. 346.

     Smith M, García-Martínez E, Pitter MR, Fucikova J, Spisek R, Zitvogel L, Kroemer G, Galluzzi L, Trial Watch: Toll-like receptor agonists in cancer immunotherapy, Oncoimmunology. 7 (2018 ) 1–15..

     Not in our library10.1080/2162402x.2018.1526250

347. 347.

     Biswas SK, Lopez-Collazo E, Endotoxin tolerance: new mechanisms, molecules and clinical significance, Trends Immunol. 30 (2009 ) 475–487..

     Not in our library10.1016/j.it.2009.07.009

348. 348.

     Chen J, Ivashkiv LB, IFN-γ abrogates endotoxin tolerance by facilitating Toll-like receptor-induced chromatin remodeling, Proc National Acad Sci. 107 (2010 ) 19438–19443..

     Not in our library10.1073/pnas.1007816107

349. 349.

     Miles K, Heaney J, Sibinska Z, Salter D, Savill J, Gray D, Gray M, A tolerogenic role for Toll-like receptor 9 is revealed by B-cell interaction with DNA complexes expressed on apoptotic cells, Proc National Acad Sci. 109 (2012 ) 887–892..

     Not in our library10.1073/pnas.1109173109

350. 350.

     Silver AC, Arjona A, Walker WE, Fikrig E, The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity, Immunity. 36 (2012 ) 251–261..

     Not in our library10.1016/j.immuni.2011.12.017

351. 351.

     Kondo T, Kawai T, Akira S, Dissecting negative regulation of Toll-like receptor signaling, Trends Immunol. 33 (2012 ) 449–458..

     Not in our library10.1016/j.it.2012.05.002

352. 352.

     Shi Y, White D, He L, Miller RL, Spaner DE, Toll-like Receptor-7 Tolerizes Malignant B Cells and Enhances Killing by Cytotoxic Agents, Cancer Res. 67 (2007 ) 1823–1831..

     Not in our library10.1158/0008-5472.can-06-2381

353. 353.

     Koga-Yamakawa E, Murata M, Dovedi SJ, Wilkinson RW, Ota Y, Umehara H, Sugaru E, Hirose Y, Harada H, Jewsbury PJ, Yamamoto S, Robinson DT, Li CJ, TLR7 tolerance is independent of the type I IFN pathway and leads to loss of anti-tumor efficacy in mice, Cancer Immunol Immunother. 64 (2015 ) 1229–1239..

     Not in our library10.1007/s00262-015-1730-4

354. 354.

     Hayashi T, Gray CS, Chan M, Tawatao RI, Ronacher L, McGargill MA, Datta SK, Carson DA, Corr M, Prevention of autoimmune disease by induction of tolerance to Toll-like receptor 7, P Natl Acad Sci Usa. 106 (2009 ) 2764–9..

     Not in our library10.1073/pnas.0813037106

355. 355.

     Poovassery JS, Bishop GA, Type I IFN Receptor and the B Cell Antigen Receptor Regulate TLR7 Responses via Distinct Molecular Mechanisms, The Journal of Immunology. 189 (2012 ) 1757–1764..

     Not in our library10.4049/jimmunol.1200624

356. 356.

     Michaelis KA, Norgard MA, Levasseur PR, Olson B, Burfeind KG, Buenafe AC, Zhu X, Jeng S, McWeeney SK, Marks DL, Persistent Toll-like receptor 7 stimulation induces behavioral and molecular innate immune tolerance, Brain Behav Immun. 82 (2019 ) 338–353..

     Not in our library10.1016/j.bbi.2019.09.004

357. 357.

     Bourquin C, Hotz C, Noerenberg D, Voelkl A, Heidegger S, Roetzer LC, Storch B, Sandholzer N, Wurzenberger C, Anz D, Endres S, Systemic Cancer Therapy with a Small Molecule Agonist of Toll-like Receptor 7 Can Be Improved by Circumventing TLR Tolerance, Cancer Research. 71 (2011 ) 5123–5133..

     Not in our library10.1158/0008-5472.can-10-3903

358. 358.

     Tsitoura D, Ambery C, Price M, Powley W, Garthside S, Biggadike K, Quint D, Early clinical evaluation of the intranasal TLR7 agonist GSK2245035: Use of translational biomarkers to guide dosing and confirm target engagement, Clin Pharmacol Ther. 98 (2015 ) 369–380..

     Not in our library10.1002/cpt.157

359. 359.

     Silver AC, Buckley SM, Hughes ME, Hastings AK, Nitabach MN, Fikrig E, Daily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells, Heliyon. 4 (2018 ) e00579..

     Not in our library10.1016/j.heliyon.2018.e00579

360. 360.

     Greenberg EN, Marshall ME, Jin S, Venkatesh S, Dragan M, Tsoi LC, Gudjonsson JE, Nie Q, Takahashi JS, Andersen B, Circadian control of interferon-sensitive gene expression in murine skin, Proc National Acad Sci. 117 (2020 ) 5761–5771..

     Not in our library10.1073/pnas.1915773117

Cited by papers we hold 3

• Vaccine adjuvants: mechanisms and platforms · 2023
  No notice
• Type I interferon-mediated tumor immunity and its role in immunotherapy · 2022
  No notice
• An Overview of Vaccine Adjuvants: Current Evidence and Future Perspectives · 2022
  No notice

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