Fc‐fusion proteins: new developments and future perspectives

Abstract

Since the first description in 1989 of CD4-Fc-fusion antagonists that inhibit human immune deficiency virus entry into T cells, Fc-fusion proteins have been intensely investigated for their effectiveness to curb a range of pathologies, with several notable recent successes coming to market. These promising outcomes have stimulated the development of novel approaches to improve their efficacy and safety, while also broadening their clinical remit to other uses such as vaccines and intravenous immunoglobulin therapy. This increased attention has also led to non-clinical applications of Fc-fusions, such as affinity reagents in microarray devices. Here we discuss recent results and more generally applicable strategies to improve Fc-fusion proteins for each application, with particular attention to the newer, less charted areas.

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    Not in our library10.1093/jb/mvj207

94. 94.

    Sidhu SS, Fellouse FA. Synthetic therapeutic antibodies. Nat Chem Biol. 2006;2:682-688.

    Not in our library10.1038/nchembio843

95. 95.

    Smith P, Dilillo DJ, Bournazos S, Li F, Ravetch JV. Mouse model recapitulating human Fcgamma receptor structural and functional diversity. Proc Natl Acad Sci USA. 2012;109:6181-6186.

    Not in our library10.1073/pnas.1203954109

96. 96.

    Soltani N, Kumar M, Glinka Y, Prud'homme GJ, Wang Q. In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes. Gene Ther. 2007;14:981-988.

    Not in our library10.1038/sj.gt.3302944

97. 97.

    Stager S, Alexander J, Kirby AC, Botto M, Rooijen NV, Smith DF, Brombacher F, Kaye PM. Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responses. Nat Med. 2003;9:1287-1292.

    Not in our library10.1038/nm933

98. 98.

    Stapleton NM, Andersen JT, Stemerding AM, Bjarnarson SP, Verheul RC, Gerritsen J, Zhao Y, Kleijer M, Sandlie I, de Haas M, et al. Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential. Nat Commun. 2011;2:599.

    Not in our library10.1038/ncomms1608

99. 99.

    Stavenhagen JB, Gorlatov S, Tuaillon N, Rankin CT, Li H, Burke S, Huang L, Johnson S, Koenig S, Bonvini E. Enhancing the potency of therapeutic monoclonal antibodies via Fc optimization. Adv Enzyme Regul. 2008;48:152-164.

    Not in our library10.1016/j.advenzreg.2007.11.011

100. 100.

     Strohl WR. Optimization of Fc-mediated effector functions of monoclonal antibodies. Curr Opin Biotechnol. 2009;20:685-691.

     Not in our library10.1016/j.copbio.2009.10.011

101. 101.

     Strohl WR, Knight DM. Discovery and development of biopharmaceuticals: current issues. Curr Opin Biotechnol. 2009;20:668-672.

     Not in our library10.1016/j.copbio.2009.10.012

102. 102.

     Suzuki T, Ishii-Watabe A, Tada M, Kobayashi T, Kanayasu-Toyoda T, Kawanishi T, Yamaguchi T. Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: a comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR. J Immunol. 2010;184:1968-1976.

     Not in our library10.4049/jimmunol.0903296

103. 103.

     Treon SP, Mitsiades C, Mitsiades N, Young G, Doss D, Schlossman R, Anderson KC. Tumor cell expression of CD59 is associated with resistance to CD20 serotherapy in patients with B-cell malignancies. J Immunother. 2001;24:263-271.

     Not in our library

104. 104.

     Van den Brande JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, van Montfrans C, Hommes DW, Peppelenbosch MP, van Deventer SJ. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology. 2003;124:1774-1785.

     Not in our library10.1016/s0016-5085(03)00382-2

105. 105.

     Van Scott MR, Mertsching E, Negrou E, Miles J, Stallings HW, Graff C, Kehry MR. Systemic administration of an Fcgamma-Fc(epsilon)-fusion protein in house dust mite sensitive nonhuman primates. Clin Immunol. 2008;128:340-348.

     Not in our library10.1016/j.clim.2008.05.001

106. 106.

     Veeramani S, Wang SY, Dahle C, Blackwell S, Jacobus L, Knutson T, Button A, Link BK, Weiner GJ. Rituximab infusion induces NK activation in lymphoma patients with the high-affinity CD16 polymorphism. Blood. 2011;118:3347-3349.

     Not in our library10.1182/blood-2011-05-351411

107. 107.

     Vire B, David A, Wiestner A. TOSO, the Fcmicro receptor, is highly expressed on chronic lymphocytic leukemia B cells, internalizes upon IgM binding, shuttles to the lysosome, and is downregulated in response to TLR activation. J Immunol. 2011;187:4040-4050.

     Not in our library10.4049/jimmunol.1100532

108. 108.

     Vollmers HP, Brandlein S. Natural IgM antibodies: the orphaned molecules in immune surveillance. Adv Drug Deliv Rev. 2006;58:755-765.

     Not in our library10.1016/j.addr.2005.08.007

109. 109.

     Wang Q, Chen K, Liu R, Zhao F, Gupta S, Zhang N, Prud'homme GJ. Novel GLP-1 fusion chimera as potent long acting GLP-1 receptor agonist. PloS one. 2010;5:e12734.

     Not in our library10.1371/journal.pone.0012734

110. 110.

     Weiner GJ. Rituximab: mechanism of action. Sem Hematol. 2010;47:115-123.

     Not in our library10.1053/j.seminhematol.2010.01.011

111. 111.

     West AP, Galimidi RP, Gnanapragasam PN, Bjorkman PJ. Single-chain Fv-based anti-HIV proteins: potential and limitations. J Virol. 2012;86:195-202.

     Not in our library10.1128/jvi.05848-11

112. 112.

     Wilson TJ, Gilfillan S, Colonna M. Fc receptor-like A associates with intracellular IgG and IgM but is dispensable for antigen-specific immune responses. J Immunol. 2010;185:2960-2967.

     Not in our library10.4049/jimmunol.1001428

113. 113.

     Wilson TJ, Fuchs A, Colonna M. Cutting edge: human FcRL4 and FcRL5 are receptors for IgA and IgG. J Immunol. 2012;188:4741-4745.

     Not in our library10.4049/jimmunol.1102651

114. 114.

     Wines BD, Trist HM, Farrugia W, Ngo C, Trowsdale J, Areschoug T, Lindahl G, Fraser JD, Ramsland PA. A conserved host and pathogen recognition site on immunoglobulins: structural and functional aspects. Adv Exp Med Biol. 2012;946:87-112.

     Not in our library10.1007/978-1-4614-0106-3_6

115. 115.

     Wojtowicz WM, Wu W, Andre I, Qian B, Baker D, Zipursky SL. A vast repertoire of Dscam binding specificities arises from modular interactions of variable Ig domains. Cell. 2007;130:1134-1145.

     Not in our library10.1016/j.cell.2007.08.026

116. 116.

     Woof JM, Burton DR. Human antibody-Fc receptor interactions illuminated by crystal structures. Nat Rev Immunol. 2004;4:89-99.

     Not in our library10.1038/nri1266

117. 117.

     Wright GJ. Signal initiation in biological systems: the properties and detection of transient extracellular protein interactions. Mol Biosyst. 2009;5:1405-1412.

     Not in our library10.1039/b903580j

118. 118.

     Ye L, Zeng R, Bai Y, Roopenian DC, Zhu X. Efficient mucosal vaccination mediated by the neonatal Fc receptor. Nat Biotechnol. 2011;29:158-163.

     Not in our library10.1038/nbt.1742

119. 119.

     Yeung YA, Leabman MK, Marvin JS, Qiu J, Adams CW, Lien S, Starovasnik MA, Lowman HB. Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates. J Immunol. 2009;182:7663-7671.

     Not in our library10.4049/jimmunol.0804182

120. 120.

     Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, Lazar GA, Roopenian DC, Desjarlais JR. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol. 2010;28:157-159.

     Not in our library10.1038/nbt.1601

121. 121.

     Zhang J, Carter J, Siu S, O'Neill JW, Gates AH, Delaney J, Mehlin C. Fusion partners as a tool for the expression of difficult proteins in mammalian cells. Curr Pharm Biotechnol. 2010;11:241-245.

     Not in our library10.2174/138920110791111898

122. 122.

     Zhu X, Meng G, Dickinson BL, Li X, Mizoguchi E, Miao L, Wang Y, Robert C, Wu B, Smith PD, et al. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. J Immunol. 2001;166:3266-3276.

     Not in our library10.4049/jimmunol.166.5.3266

Cited by papers we hold 5

• Biophysical differences in IgG1 Fc-based therapeutics relate to their cellular handling, interaction with FcRn and plasma half-life · 2022
  Not checked
• The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies · 2021
  No notice
• Antibody Structure and Function: The Basis for Engineering Therapeutics · 2019
  No notice
• Single-Domain Antibodies and Their Formatting to Combat Viral Infections · 2018
  Not checked
• Recombinant HSA-CMG2 Is a Promising Anthrax Toxin Inhibitor · 2016
  Not checked

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