Immune suppression in cynomolgus monkeys by XPro9523: An improved CTLA4-Ig fusion with enhanced binding to CD80, CD86 and neonatal Fc receptor FcRn

mAbs

Volumn 5, Issue 3, 2013, Pages 384-396

  Bernett, Matthew J ^a   Chu, Seung Y ^a   Leung, Irene ^a   Moore, Gregory L ^a   Lee, Sung Hyung ^a   Pong, Erik ^a   Chen, Hsing ^a   Phung, Sheryl ^a   Muchhal, Umesh S ^a   Horton, Holly M ^a   Lazar, Greg A ^a   Desjarlais, John R ^a   Szymkowski, David E ^a  

^a Xencor Inc   (United States)

Author keywords

Abatacept; Belatacept; Biosuperior; CD80; CD86; CTLA4 Ig; Fc engineering; FcRn; Rheumatoid arthritis; Transplantation

Indexed keywords

ABATACEPT; B7 ANTIGEN; BELATACEPT; CD86 ANTIGEN; CTLA 4G; FC RECEPTOR; IMMUNOGLOBULIN G; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN M; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 2; UNCLASSIFIED DRUG; XPRO 9523; XPRO9523; ANTIBODY CONJUGATE; FC RECEPTOR, NEONATAL; HLA ANTIGEN CLASS 1; HYBRID PROTEIN; PROTEIN BINDING;

ANIMAL EXPERIMENT; ARTHRITIS; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; CYNOMOLGUS MONKEY; CYTOKINE PRODUCTION; DRUG POTENCY; HAPLORHINI; IMMUNOSUPPRESSIVE TREATMENT; INFLAMMATION; LYMPHOCYTE PROLIFERATION; NONHUMAN; PROTEIN ENGINEERING; RHEUMATOID ARTHRITIS; SUBSTITUTION REACTION; T LYMPHOCYTE; ANIMAL; ANTIBODY AFFINITY; ANTIBODY PRODUCTION; ARTHRITIS, EXPERIMENTAL; ARTHRITIS, RHEUMATOID; CELL CULTURE; DBA MOUSE; DRUG EFFECTS; FEMALE; GENETICS; GRAFT REJECTION; HUMAN; IMMUNOLOGY; KIDNEY TRANSPLANTATION; LYMPHOCYTE ACTIVATION; MACACA FASCICULARIS; MALE; METABOLISM; MOUSE; MUTATION; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIBODY AFFINITY; ANTIBODY FORMATION; ANTIGENS, CD80; ANTIGENS, CD86; ARTHRITIS, EXPERIMENTAL; ARTHRITIS, RHEUMATOID; CELLS, CULTURED; FEMALE; GRAFT REJECTION; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IMMUNOCONJUGATES; IMMUNOSUPPRESSION; KIDNEY TRANSPLANTATION; LYMPHOCYTE ACTIVATION; MACACA FASCICULARIS; MALE; MICE; MICE, INBRED DBA; MUTATION; PROTEIN BINDING; PROTEIN ENGINEERING; RECEPTORS, FC; RECOMBINANT FUSION PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84877899298     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.4161/mabs.23976     Document Type: Article

References (30)

1. Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 2001; 19:565-94; PMID:11244047; http://dx.doi.org/10.1146/annurev.immunol.19.1.565
2. Lafferty KJ, Prowse SJ, Simeonovic CJ, Warren HS. Immunobiology of tissue transplantation: a return to the passenger leukocyte concept. Annu Rev Immunol 1983; 1:143-73; PMID:6443557; http://dx.doi. org/10.1146/annurev.iy.01.040183. 001043
3. Lafferty KJ, Woolnough J. The origin and mechanism of the allograft reaction. Immunol Rev 1977; 35:231-62; PMID:330389; http://dx.doi.org/10.1111/j. 1600-065X.1977.tb00241.x
4. Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol 2011; 11:852-63; PMID:22116087; http://dx.doi.org/10.1038/nri3108
5. Wing K, Yamaguchi T, Sakaguchi S. Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation. Trends Immunol 2011; 32:428-33; PMID:21723783; http://dx.doi.org/10.1016/j. it.2011.06.002
6. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med 1991; 174:561-9; PMID:1714933; http://dx.doi. org/10.1084/jem.174.3.561
7. Vincenti F. Costimulation blockade in autoimmunity and transplantation. J Allergy Clin Immunol 2008; 121:299-306, quiz 307-8; PMID:18269922; http://dx.doi.org/10.1016/j.jaci.2008.01.002
8. Larsen CP, Pearson TC, Adams AB, Tso P, Shirasugi N, Strobert E, et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 2005; 5:443-53; PMID:15707398; http://dx.doi. org/10.1111/j.1600-6143.2005.00749.x
9. Davis PM, Abraham R, Xu L, Nadler SG, Suchard SJ. Abatacept binds to the Fc receptor CD64 but does not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity. J Rheumatol 2007; 34:2204-10; PMID:17787038
10. World Health Organization. Recommended International Nonproprietary Names: List 59. WHO Drug Information 2008; 22:41-76
11. Leister KJ, Schaefer EJ, Bates RC, Bramhall EA, Didio DM, Donaldson R, et al. (Bristol-Myers Squibb Company). Compositions and methods for producing a composition. United States Patent and Trademark Office 2009; US 20090252749A1
12. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007; 7:715-25; PMID:17703228; http://dx.doi.org/10.1038/nri2155
13. Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, et al. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 2010; 28:157-9; PMID:20081867; http://dx.doi. org/10.1038/nbt.1601
14. Kuo TT, Aveson VG. Neonatal Fc receptor and IgG-based therapeutics. MAbs 2011; 3:422-30; PMID:22048693; http://dx.doi.org/10.4161/mabs.3.5.16983
15. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1994; 1:793-801; PMID:7534620; http://dx.doi.org/10.1016/S1074-7613(94)80021-9
16. Xu Z, Juan V, Ivanov A, Ma Z, Polakoff D, Powers DB, et al. Affinity and cross-reactivity engineering of CTLA4-Ig to modulate T cell costimulation. J Immunol 2012; 189:4470-7; PMID:23018459; http://dx.doi.org/10.4049/jimmunol. 1201813
17. Schwartz JC, Zhang X, Fedorov AA, Nathenson SG, Almo SC. Structural basis for co-stimulation by the human CTLA-4/B7-2 complex. Nature 2001; 410:604-8; PMID:11279501; http://dx.doi. org/10.1038/35069112
18. Stamper CC, Zhang Y, Tobin JF, Erbe DV, Ikemizu S, Davis SJ, et al. Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature 2001; 410:608-11; PMID:11279502; http://dx.doi.org/10.1038/ 35069118
19. Kliwinski C, Kukral D, Postelnek J, Krishnan B, Killar L, Lewin A, et al. Prophylactic administration of abatacept prevents disease and bone destruction in a rat model of collagen-induced arthritis. J Autoimmun 2005; 25:165-71; PMID:16256307; http://dx.doi. org/10.1016/j.jaut.2005.09.020
20. Knoerzer DB, Karr RW, Schwartz BD, Mengle-Gaw LJ. Collagen-induced arthritis in the BB rat. Prevention of disease by treatment with CTLA-4-Ig. J Clin Invest 1995; 96:987-93; PMID:7543497; http://dx.doi. org/10.1172/JCI118146
21. Finck BK, Linsley PS, Wofsy D. Treatment of murine lupus with CTLA4Ig. Science 1994; 265:1225-7; PMID:7520604; http://dx.doi.org/10.1126/science. 7520604
22. Dall'Acqua WF, Woods RM, Ward ES, Palaszynski SR, Patel NK, Brewah YA, et al. Increasing the affinity of a human IgG1 for the neonatal Fc receptor: biological consequences. J Immunol 2002; 169:5171-80; PMID:12391234
23. Levisetti MG, Padrid PA, Szot GL, Mittal N, Meehan SM, Wardrip CL, et al. Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation. J Immunol 1997; 159:5187-91; PMID:9548454
24. Bristol-Myers Squibb. ORENCIA (package insert). Princeton, New Jersey, USA, 2011
25. Bristol-Myers Squibb. NULOJIX (package insert). Princeton, New Jersey, USA, 2011
26. Genovese MC, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, et al. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum 2011; 63:2854-64; PMID:21618201; http://dx.doi.org/10.1002/art. 30463
27. Bristol-Myers Squibb. Belatacept (BMS-224818): briefing document for March 2010 meeting (BLA 125288). FDA Cardiovascular and Renal Drugs Advisory Committee, 2010
28. Kirk AD, Harlan DM, Armstrong NN, Davis TA, Dong Y, Gray GS, et al. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci U S A 1997; 94:8789-94; PMID:9238056; http://dx.doi.org/10. 1073/pnas.94.16.8789
29. Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, et al. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eightyfive days after the first infusion. Arthritis Rheum 2002; 46:1470-9; PMID:12115176; http://dx.doi. org/10.1002/art.10294
30. Brand DD, Latham KA, Rosloniec EF. Collageninduced arthritis. Nat Protoc 2007; 2:1269-75; PMID:17546023; http://dx.doi.org/10.1038/nprot.2007.173