New directions for half-life extension of protein therapeutics: The rise of antibody Fc domains and fragments

Current Pharmaceutical Biotechnology

Volumn 17, Issue 15, 2016, Pages 1348-1352

  Wang, Lili ^a   Ying, Tianlei ^a  

^a FUDAN UNIVERSITY   (China)

Author keywords

Antibody fragments; FcRn; Half life; IgG1 CH2; IgG1 CH3; IgG1 Fc; Protein therapeutics

Indexed keywords

BEVACIZUMAB; FC RECEPTOR; IMMUNOGLOBULIN G1; TUMOR NECROSIS FACTOR RECEPTOR; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2;

CH2 DOMAIN; CH3 DOMAIN; CHEMICAL REACTION; DIMERIZATION; ESCHERICHIA COLI; HALF LIFE TIME; HUMAN; MELTING POINT; MUTAGENESIS; NONHUMAN; PH; PHYSICAL CHEMISTRY; PROTEIN BINDING; PROTEIN EXPRESSION; REVIEW; SIZE EXCLUSION CHROMATOGRAPHY; TEMPERATURE;

EID: 85009209257     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/1389201017666160823144032     Document Type: Review

References (54)

1. Dimitrov, D.S. Therapeutic proteins. Methods Molecul. Biol., 2012, 899, 1-26
2. Leurs, U.; Mistarz, U.H.; Rand, K.D. Getting to the core of protein pharmaceuticals-Comprehensive structure analysis by mass spectrometry. Eur. J. Pharm. Biopharm., 2015, 93, 95-109.
3. Rader, R.A. (Re)defining biopharmaceutical. Nat. Biotechnol., 2008, 26(7), 743-751
4. Walsh, G., Biopharmaceutical benchmarks 2010. Nat. Biotechnol., 2010, 28(9), 917-924.
5. Rath, T.; Baker, K.; Dumont, J.A.; Peters, R.T.; Jiang, H.; Qiao, S.W.; Lencer, W.I.; Pierce, G.F.; Blumberg, R.S. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit. Rev. Biotechnol., 2013
6. Sleep, D.; Cameron, J.; Evans, L.R. Albumin as a versatile platform for drug half-life extension. Biochim. Et Biophysic. Acta, 2013, 1830(12), 5526-5534
7. Gaberc-Porekar, V.; Zore, I.; Podobnik, B.; Menart, V. Obstacles and pitfalls in the PEGylation of therapeutic proteins. Curr. Opin. Drug Discov. Developm., 2008, 11(2), 242-250.
8. Kuo, T.T.; Aveson, V.G. Neonatal Fc receptor and IgG-based therapeutics. mAbs, 2011, 3(5), 422-430
9. Kuo, T.T.; Baker, K.; Yoshida, M.; Qiao, S.W.; Aveson, V.G.; Lencer, W.I.; Blumberg, R.S. Neonatal Fc receptor: from immunity to therapeutics. J. Clin. Immunol., 2010, 30(6), 777-789
10. Roopenian, D.C.; Akilesh, S. FcRn: The neonatal Fc receptor comes of age. Nat. Rev. Immunol., 2007, 7(9), 715-725.
11. Kontermann, R.E. Strategies for extended serum half-life of protein therapeutics. Curr. Opin. Biotechnol., 2011, 22(6), 868-876.
12. Chen, W.; Gong, R.; Ying, T.; Prabakaran, P.; Zhu, Z.; Feng, Y.; Dimitrov, D.S. Discovery of novel candidate therapeutics and diagnostics based on engineered human antibody domains. Curr. Drug Discov. Technologies, 2014, 11(1), 28-40
13. Holliger, P.; Hudson, P.J. Engineered antibody fragments and the rise of single domains. Nat. Biotechnol., 2005, 23(9), 1126-1136
14. Nelson, A.L.; Reichert, J.M. Development trends for therapeutic antibody fragments. Nat. Biotechnol., 2009, 27(4), 331-337
15. Saerens, D.; Ghassabeh, G.H.; Muyldermans, S. Single-domain antibodies as building blocks for novel therapeutics. Curr. Opin. Pharmacol., 2008, 8(5), 600-608.
16. Nelson, A.L.; Dhimolea, E.; Reichert, J.M. Development trends for human monoclonal antibody therapeutics. Nat. Rev. Drug Discov., 2010, 9(10), 767-774.
17. Labrijn, A.F.; Poignard, P.; Raja, A.; Zwick, M.B.; Delgado, K.; Franti, M.; Binley, J.; Vivona, V.; Grundner, C.; Huang, C.C.; Venturi, M.; Petropoulos, C.J.; Wrin, T.; Dimitrov, D.S.; Robinson, J.; Kwong, P.D.; Wyatt, R.T.; Sodroski, J.; Burton, D.R. Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary human immunodeficiency virus type 1. J. Virol., 2003, 77(19), 10557-10565
18. Chen, W.; Zhu, Z.; Feng, Y.; Dimitrov, D.S. Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers. Proc. Natl. Acad. Sci. USA, 2008, 105(44), 17121-17126
19. Binz, H.K.; Amstutz, P.; Pluckthun, A. Engineering novel binding proteins from nonimmunoglobulin domains. Nat. Biotechnol., 2005, 23(10), 1257-1268.
20. Yokota, T.; Milenic, D.E.; Whitlow, M.; Schlom, J. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res., 1992, 52(12), 3402-3408
21. Nelson, A.L. Antibody fragments: Hope and hype. mAbs 2010, 2(1), 77-83
22. Thurber, G.M.; Schmidt, M.M.; Wittrup, K.D. Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Adv. Drug Deliv. Rev., 2008, 60(12), 1421-1434
23. Chames, P.; Van Regenmortel, M.; Weiss, E.; Baty, D. Therapeutic antibodies: Successes, limitations and hopes for the future. Brit. J. Pharmacology, 2009, 157(2), 220-233
24. Batra, S.K.; Jain, M.; Wittel, U.A.; Chauhan, S.C.; Colcher, D. Pharmacokinetics and biodistribution of genetically engineered antibodies. Curr. Opin. Biotechnol., 2002, 13(6), 603-608.
25. Huber, A.H.; Kelley, R.F.; Gastinel, L.N.; Bjorkman, P.J. Crystallization and stoichiometry of binding of a complex between a rat intestinal Fc receptor and Fc. J. Mol. Biol., 1993, 230(3), 1077-1083
26. Martin, W.L.; West, A.P., Jr.; Gan, L.; Bjorkman, P.J. Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: Mechanism of pH-dependent binding. Molecul. Cell, 2001, 7(4), 867-877.
27. Nimmerjahn, F.; Ravetch, J.V. Fc gamma receptors as regulators of immune responses. Nat. Rev. Immunol., 2008, 8(1), 34-47.
28. Strohl, W.R. Optimization of Fc-mediated effector functions of monoclonal antibodies. Curr. Opin. Biotechnol., 2009, 20(6), 685-691
29. Lazar, G.A.; Dang, W.; Karki, S.; Vafa, O.; Peng, J.S.; Hyun, L.; Chan, C.; Chung, H.S.; Eivazi, A.; Yoder, S.C.; Vielmetter, J.; Carmichael, D.F.; Hayes, R.J.; Dahiyat, B.I. Engineered antibody Fc variants with enhanced effector function. Proc. Natl. Acad. Sci. USA, 2006, 103(11), 4005-4010
30. Kubota, T.; Niwa, R.; Satoh, M.; Akinaga, S.; Shitara, K.; Hanai, N. Engineered therapeutic antibodies with improved effector functions. Cancer Sci., 2009, 100(9), 1566-1572.
31. Ko, S.Y.; Pegu, A.; Rudicell, R.S.; Yang, Z.Y.; Joyce, M.G.; Chen, X.; Wang, K.; Bao, S.; Kraemer, T.D.; Rath, T.; Zeng, M.; Schmidt, S.D.; Todd, J.P.; Penzak, S.R.; Saunders, K.O.; Nason, M. C.; Haase, A.T.; Rao, S.S.; Blumberg, R.S.; Mascola, J.R.; Nabel, G.J. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature, 2014, 514(7524), 642-645
32. Zalevsky, J.; Chamberlain, A.K.; Horton, H.M.; Karki, S.; Leung, I.W.; Sproule, T.J.; Lazar, G.A.; Roopenian, D.C.; Desjarlais, J.R. Enhanced antibody half-life improves in vivo activity. Nat. Biotechnol., 2010, 28(2), 157-159.
33. Ying, T.; Gong, R.; Ju, T.W.; Prabakaran, P.; Dimitrov, D.S. Engineered Fc based antibody domains and fragments as novel scaffolds. Biochim. Et Biophysic. Acta, 2014, 1844(11), 1977-1982.
34. Gurbaxani, B.; Dela Cruz, L.L.; Chintalacharuvu, K.; Morrison, S.L. Analysis of a family of antibodies with different half-lives in mice fails to find a correlation between affinity for FcRn and serum half-life. Mol. Immunol., 2006, 43(9), 1462-1473
35. Dall'Acqua, W.F.; Kiener, P.A.; Wu, H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J. Biologic. Chem., 2006, 281(33), 23514-24
36. Hinton, P.R.; Johlfs, M.G.; Xiong, J.M.; Hanestad, K.; Ong, K.C.; Bullock, C.; Keller, S.; Tang, M.T.; Tso, J.Y.; Vasquez, M.; Tsurushita, N. Engineered human IgG antibodies with longer serum half-lives in primates. J. Biologic. Chem., 2004, 279(8), 6213-6216
37. Hinton, P.R.; Xiong, J.M.; Johlfs, M.G.; Tang, M.T.; Keller, S.; Tsurushita, N. An engineered human IgG1 antibody with longer serum half-life. J Immunol., 2006, 176(1), 346-56
38. Yeung, Y.A.; Leabman, M.K.; Marvin, J.S.; Qiu, J.; Adams, C.W.; Lien, S.; Starovasnik, M.A.; Lowman, H.B. Engineering human IgG1 affinity to human neonatal Fc receptor: Impact of affinity improvement on pharmacokinetics in primates. J. Immunol., 2009, 182(12), 7663-7671.
39. Datta-Mannan, A.; Chow, C.K.; Dickinson, C.; Driver, D.; Lu, J.; Witcher, D.R.; Wroblewski, V.J. FcRn affinity-pharmacokinetic relationship of five human IgG4 antibodies engineered for improved in vitro FcRn binding properties in cynomolgus monkeys. Drug Metabolism Disposition: The Biologic. Fate Chemicals, 2012, 40(8), 1545-1555
40. Datta-Mannan, A.; Witcher, D.R.; Tang, Y.; Watkins, J.; Jiang, W.; Wroblewski, V.J. Humanized IgG1 variants with differential binding properties to the neonatal Fc receptor: Relationship to pharmacokinetics in mice and primates. Drug Metabolism Disposition: Biologic. Fate Chemic., 2007, 35(1), 86-94
41. Vaccaro, C.; Zhou, J.; Ober, R.J.; Ward, E.S. Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Nat. Biotechnol., 2005, 23(10), 1283-1288.
42. Dumont, J.A.; Low, S.C.; Peters, R.T.; Bitonti, A.J. Monomeric Fc fusions: Impact on pharmacokinetic and biological activity of protein therapeutics. BioDrugs: Clin. immunotherapeut. Biopharmaceut. Gene Therap., 2006, 20(3), 151-160.
43. Peters, R. T.; Low, S.C.; Kamphaus, G. D.; Dumont, J.A.; Amari, J.V.; Lu, Q.; Zarbis-Papastoitsis, G.; Reidy, T.J.; Merricks, E.P.; Nichols, T.C.; Bitonti, A.J. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood, 2010, 115(10), 2057-2064.
44. Deisenhofer, J. Crystallographic refinement and atomic models of a human Fc fragment and its complex with fragment B of protein A from Staphylococcus aureus at 2.9-and 2.8-A resolution. Biochemistry, 1981, 20(9), 2361-2370
45. Miller, S. Protein-protein recognition and the association of immunoglobulin constant domains. J. Mol. Biol., 1990, 216(4), 965-973.
46. Ying, T.; Chen, W.; Gong, R.; Feng, Y.; Dimitrov, D.S. Soluble monomeric IgG1 Fc. J. Biologic. Chem., 2012, 287(23), 19399-19408
47. Ishino, T.; Wang, M.; Mosyak, L.; Tam, A.; Duan, W.; Svenson, K.; Joyce, A.; O'Hara, D.M.; Lin, L.; Somers, W.S.; Kriz, R. Engineering a monomeric Fc domain modality by Nglycosylation for the half-life extension of biotherapeutics. J. Biologic. Chem., 2013, 288(23), 16529-16537.
48. Ying, T.; Feng, Y.; Wang, Y.; Chen, W.; Dimitrov, D.S. Monomeric IgG1 Fc molecules displaying unique Fc receptor interactions that are exploitable to treat inflammation-mediated diseases. mAbs, 2014, 6(5), 1201-1210.
49. Ying, T.; Ju, T.W.; Wang, Y.; Prabakaran, P.; Dimitrov, D.S. Interactions of IgG1 CH2 and CH3 Domains with FcRn. Front. Immunol., 2014, 5, 146.
50. Yasmeen, D.; Ellerson, J.R.; Dorrington, K.J.; Painter, R.H. The structure and function of immunoglobulin domains. IV. The distribution of some effector functions among the Cgamma2 and Cgamma3 homology regions of human immunoglobulin G1. J. Immunol., 1976, 116(2), 518-526
51. Ellerson, J.R.; Yasmeen, D.; Painter, R.H.; Dorrington, K.J. A fragment corresponding to the C(H)2 region of immunoglobulin G (IgG) with complement fixing activity. FEBS Lett., 1972, 24(3), 318-322.
52. Gong, R.; Wang, Y.; Feng, Y.; Zhao, Q.; Dimitrov, D.S. Shortened engineered human antibody CH2 domains: Increased stability and binding to the human neonatal Fc receptor. J. Biologic. Chem., 2011, 286(31), 27288-27293.
53. Gehlsen, K.; Gong, R.; Bramhill, D.; Wiersma, D.; Kirkpatrick, S.; Wang, Y.; Feng, Y.; Dimitrov, D.S. Pharmacokinetics of engineered human monomeric and dimeric CH2 domains. MAbs 2012, 4(4), 466-474.
54. Ying, T.; Chen, W.; Feng, Y.; Wang, Y.; Gong, R.; Dimitrov, D.S. Engineered soluble monomeric IgG1 CH3 domain: Generation, mechanisms of function, and implications for design of biological therapeutics. J. Biologic. Chem., 2013, 288(35), 25154-25164.