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Fc‐fusion proteins: new developments and future perspectives

Daniel M. Czajkowsky, Jun Hu, Zhifeng Shao and 1 more

EMBO Molecular Medicine · 2012 · Review · CC BY-NC

doi:10.1002/emmm.201201379

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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References 122

  1. 1.

    Adachi T, Harumiya S, Takematsu H, Kozutsumi Y, Wabl M, Fujimoto M, Tedder TF. CD22 serves as a receptor for soluble IgM. Eur J Immunol. 2011;42:241-247.

    Not in our library10.1002/eji.201141899

  2. 2.

    Ammann JU, Jahnke M, Dyson MR, Kaufman J, Trowsdale J. Detection of weak receptor-ligand interactions using IgM and J-chain-based fusion proteins. Eur J Immunol. 2012;42:1354-1356.

    Not in our library10.1002/eji.201142151

  3. 3.

    Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature. 2011;475:110-113.

    Not in our library10.1038/nature10134

  4. 4.

    Arnason JE, Campigotto F, Neuberg D, Bussel JB. Abnormalities in IgA and IgM are associated with treatment-resistant ITP. Blood. 2012;119:5016-5020.

    Not in our library10.1182/blood-2011-09-381020

  5. 5.

    Bajtay Z, Csomor E, Sandor N, Erdei A. Expression and role of Fc- and complement-receptors on human dendritic cells. Immunol Lett. 2006;104:46-52.

    Not in our library10.1016/j.imlet.2005.11.023

  6. 6.

    Bakema JE, van Egmond M. The human immunoglobulin A Fc receptor FcalphaRI: a multifaceted regulator of mucosal immunity. Mucosal Immunol. 2011a;4:612-624.

    Not in our library10.1038/mi.2011.36

  7. 7.

    Bakema JE, van Egmond M. Immunoglobulin A: a next generation of therapeutic antibodies. MAbs. 2011b;3:352-361.

    Not in our library10.4161/mabs.3.4.16092

  8. 8.

    Bakema JE, Ganzevles SH, Fluitsma DM, Schilham MW, Beelen RH, Valerius T, Lohse S, Glennie MJ, Medema JP, van Egmond M. Targeting FcalphaRI on polymorphonuclear cells induces tumor cell killing through autophagy. J Immunol. 2011;187:726-732.

    Not in our library10.4049/jimmunol.1002581

  9. 9.

    Baker K, Qiao SW, Kuo TT, Aveson VG, Platzer B, Andersen JT, Sandlie I, Chen Z, de Haar C, Lencer WI, et al. Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8-CD11b+ dendritic cells. Proc Natl Acad Sci USA. 2011;108:9927-9932.

    Not in our library10.1073/pnas.1019037108

  10. 10.

    Balu S, Reljic R, Lewis MJ, Pleass RJ, McIntosh R, van Kooten C, van Egmond M, Challacombe S, Woof JM, Ivanyi J. A novel human IgA monoclonal antibody protects against tuberculosis. J Immunol. 2011;186:3113-3119.

    Not in our library10.4049/jimmunol.1003189

  11. 11.

    Beck A, Reichert JM. Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies. MAbs. 2011;3:415-416.

    Not in our library10.4161/mabs.3.5.17334

  12. 12.

    Biburger M, Aschermann S, Schwab I, Lux A, Albert H, Danzer H, Woigk M, Dudziak D, Nimmerjahn F. Monocyte subsets responsible for immunoglobulin G-dependent effector functions in vivo. Immunity. 2011;35:932-944.

    Not in our library10.1016/j.immuni.2011.11.009

  13. 13.

    Bitonti AJ, Dumont JA, Low SC, Peters RT, Kropp KE, Palombella VJ, Stattel JM, Lu Y, Tan CA, Song JJ, et al. Pulmonary delivery of an erythropoietin Fc fusion protein in non-human primates through an immunoglobulin transport pathway. Proc Natl Acad Sci USA. 2004;101:9763-9768.

    Not in our library10.1073/pnas.0403235101

  14. 14.

    Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, Daeron M. Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood. 2009;113:3716-3725.

    Not in our library10.1182/blood-2008-09-179754

  15. 15.

    Canal F, Sanchis J, Vicent MJ. Polymer–drug conjugates as nano-sized medicines. Curr Opin Biotechnol. 2011;22:894-900.

    Not in our library10.1016/j.copbio.2011.06.003

  16. 16.

    Capon DJ, Chamow SM, Mordenti J, Marsters SA, Gregory T, Mitsuya H, Byrn RA, Lucas C, Wurm FM, Groopman JE, et al. Designing CD4 immunoadhesins for AIDS therapy. Nature. 1989;337:525-531.

    Not in our library10.1038/337525a0

  17. 17.

    Carrillo-Conde B, Song EH, Chavez-Santoscoy A, Phanse Y, Ramer-Tait AE, Pohl NL, Wannemuehler MJ, Bellaire BH, Narasimhan B. Mannose-functionalized “pathogen-like” polyanhydride nanoparticles target C-type lectin receptors on dendritic cells. Mol Pharm. 2011;8:1877-1886.

    Not in our library10.1021/mp200213r

  18. 18.

    Carter PJ. Introduction to current and future protein therapeutics: a protein engineering perspective. Exp Cell Res. 2011;317:1261-1269.

    Not in our library10.1016/j.yexcr.2011.02.013

  19. 19.

    Cervenak J, Bender B, Schneider Z, Magna M, Carstea BV, Liliom K, Erdei A, Bosze Z, Kacskovics I. Neonatal FcR overexpression boosts humoral immune response in transgenic mice. J Immunol. 2011;186:959-968.

    Not in our library10.4049/jimmunol.1000353

  20. 20.

    Congy-Jolivet N, Probst A, Watier H, Thibault G. Recombinant therapeutic monoclonal antibodies: mechanisms of action in relation to structural and functional duality. Crit Rev Oncol/Hematol. 2007;64:226-233.

    Not in our library10.1016/j.critrevonc.2007.06.013

  21. 21.

    Cox GN, Smith DJ, Carlson SJ, Bendele AM, Chlipala EA, Doherty DH. Enhanced circulating half-life and hematopoietic properties of a human granulocyte colony-stimulating factor/immunoglobulin fusion protein. Exp Hematol. 2004;32:441-449.

    Not in our library10.1016/j.exphem.2004.01.012

  22. 22.

    Czajkowsky DM, Salanti A, Ditlev SB, Shao Z, Ghumra A, Rowe JA, Pleass RJ. IgM, Fc mu Rs, and malarial immune evasion. J Immunol. 2010;184:4597-4603.

    Not in our library10.4049/jimmunol.1000203

  23. 23.

    Daeron M, Malbec O, Latour S, Arock M, Fridman WH. Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. J Clin Invest. 1995;95:577-585.

    Not in our library10.1172/jci117701

  24. 24.

    Dall'Acqua WF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem. 2006;281:23514-23524.

    Not in our library10.1074/jbc.m604292200

  25. 25.

    Davis JH, Aperlo C, Li Y, Kurosawa E, Lan Y, Lo KM, Huston JS. SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. Protein Eng Des Sel. 2010;23:195-202.

    Not in our library10.1093/protein/gzp094

  26. 26.

    Flanagan ML, Arias RS, Hu P, Khawli LA, Epstein AL. Soluble Fc fusion proteins for biomedical research. Methods Mol Biol. 2007;378:33-52.

    Not in our library10.1007/978-1-59745-323-3_3

  27. 27.

    Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, Verger D, Fontecilla-Camps JC, Arlaud GJ. The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem. 2003;278:46974-46982.

    Not in our library10.1074/jbc.m307764200

  28. 28.

    Getahun A, Heyman B. How antibodies act as natural adjuvants. Immunol Lett. 2006;104:38-45.

    Not in our library10.1016/j.imlet.2005.11.005

  29. 29.

    Getahun A, Dahlstrom J, Wernersson S, Heyman B. IgG2a-mediated enhancement of antibody and T cell responses and its relation to inhibitory and activating Fc gamma receptors. J Immunol. 2004;172:5269-5276.

    Not in our library10.4049/jimmunol.172.9.5269

  30. 30.

    Gil M, Bieniasz M, Wierzbicki A, Bambach BJ, Rokita H, Kozbor D. Targeting a mimotope vaccine to activating Fcgamma receptors empowers dendritic cells to prime specific CD8+ T cell responses in tumor-bearing mice. J Immunol. 2009;183:6808-6818.

    Not in our library10.4049/jimmunol.0900364

  31. 31.

    Gonzalez LC, Loyet KM, Calemine-Fenaux J, Chauhan V, Wranik B, Ouyang W, Eaton DL. A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator. Proc Natl Acad Sci USA. 2005;102:1116-1121.

    Not in our library10.1073/pnas.0409071102

  32. 32.

    Griffiss JM, Goroff DK. IgA blocks IgM and IgG-initiated immune lysis by separate molecular mechanisms. J Immunol. 1983;130:2882-2885.

    Not in our library

  33. 33.

    Harte PG, Cooke A, Playfair JH. Specific monoclonal IgM is a potent adjuvant in murine malaria vaccination. Nature. 1983;302:256-258.

    Not in our library10.1038/302256a0

  34. 34.

    Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, Evans DT, Montefiori DC, Karnasuta C, Sutthent R, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366:1275-1286.

    Not in our library10.1056/nejmoa1113425

  35. 35.

    Heldwein EE, Krummenacher C. Entry of herpesviruses into mammalian cells. Cell Mol Life Sci. 2008;65:1653-1668.

    Not in our library10.1007/s00018-008-7570-z

  36. 36.

    Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, Weinstein SP, Belomestnov P, Yancopoulos GD, Stahl N, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58:2443-2452.

    Not in our library10.1002/art.23687

  37. 37.

    Horiuchi T, Mitoma H, Harashima S, Tsukamoto H, Shimoda T. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford). 2010;49:1215-1228.

    Not in our library10.1093/rheumatology/keq031

  38. 38.

    Hsu TL, Cheng SC, Yang WB, Chin SW, Chen BH, Huang MT, Hsieh SL, Wong CH. Profiling carbohydrate-receptor interaction with recombinant innate immunity receptor-Fc fusion proteins. J Biol Chem. 2009;284:34479-34489.

    Not in our library10.1074/jbc.m109.065961

  39. 39.

    Huang C. Receptor-Fc fusion therapeutics, traps, and MIMETIBODY technology. Curr Opin Biotechnol. 2009;20:692-699.

    Not in our library10.1016/j.copbio.2009.10.010

  40. 40.

    Idusogie EE, Wong PY, Presta LG, Gazzano-Santoro H, Totpal K, Ultsch M, Mulkerrin MG. Engineered antibodies with increased activity to recruit complement. J Immunol. 2001;166:2571-2575.

    Not in our library10.4049/jimmunol.166.4.2571

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