Chronic administration of belatacept, a T-cell costimulatory signal blocker, in cynomolgus monkeys

Toxicological Sciences

Volumn 127, Issue 1, 2012, Pages 159-168

  Haggerty, Helen G ^a   Proctor, Stanley J ^b  

^a BRISTOL MYERS SQUIBB   (United States)

^b JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Belatacept; Costimulation; Immunosuppression; Kidney transplant; Monkeys; Nephrotoxicity; Organ transplant; Toxicity; Toxicokinetics

Indexed keywords

BELATACEPT; CD28 ANTIGEN; IMMUNOGLOBULIN G; KEYHOLE LIMPET HEMOCYANIN; SODIUM CHLORIDE;

ANIMAL EXPERIMENT; ANTIBODY RESPONSE; ARTICLE; CONTROLLED STUDY; DRUG ACCUMULATION; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; GERMINAL CENTER; GRAFT RECIPIENT; IMMUNE SYSTEM; IMMUNIZATION; IMMUNOGLOBULIN BLOOD LEVEL; KIDNEY TRANSPLANTATION; LYMPH NODE; MACACA FASCICULARIS; MAINTENANCE DRUG DOSE; MALE; NONHUMAN; RANDOMIZED CONTROLLED TRIAL; T LYMPHOCYTE ACTIVATION; TOXICOKINETICS;

EID: 84860157541     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfs081     Document Type: Article

References (45)

1. Allen, U., and Preiksaitis, J. (2009). Epstein-Barr virus and posttransplant lymphoproliferative disorder in solid organ transplant recipients. Am. J. Transplant. 9 (Suppl. 4), S87-S96.
2. Andreoni, K. A., Brayman, K. L., Guidinger, M. K., Sommers, C. M., and Sung, R. S. (2007). Kidney and pancreas transplantation in the United States, 1996-2005. Am. J. Transplant. 7, 1359-1375.
3. Bing, P., Maode, L., Li, F., and Sheng, H. (2006). Comparison of expression of TGF-beta1, its receptors TGFbeta1R-I and TGFbeta1R-II in rat kidneys during chronic nephropathy induced by cyclosporine and tacrolimus. Transplant. Proc. 38, 2180-2182.
4. Bluestone, J. A., Liu, W., Yabu, J. M., Laszik, Z. G., Putnam, A., Belingheri, M., Gross, D. M., Townsend, R. M., and Vincenti, F. (2008). The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation. Am. J. Transplant. 8, 2086-2096.
5. Bristol-Myers Squibb. (1998). Data on File BMS-224818: Single-Dose Intravenous Toxicity and Toxicokinetics Study in Monkeys (98642, Report) Bristol-Myers Squibb Company, Syracuse, NY, DCN 910069252.
6. Brunner, M. C., Chambers, C. A., Chan, F. K., Hanke, J., Winoto, A., and Allison, J. P. (1999). CTLA-4-Mediated inhibition of early events of T cell proliferation. J. Immunol. 162, 5813-5820.
7. Chavez, H., Beaudreuil, S., Abbed, K., Taoufic, Y., Kriaa, F., Charpentier, B., and Durrbach, A. (2007). Absence of CD4CD25 regulatory T cell expansion in renal transplanted patients treated in vivo with Belatacept mediated CD28-CD80/86 blockade. Transpl. Immunol. 17, 243-248.
8. Daar, A. S., Pingle, S., Naiem, M., and Masri, M. A. (1987). Histologic changes in atrophic spleens of mice treated with cyclosporine A. Transplant. Proc. 19, 4329-4330.
9. Durrbach, A., Pestana, J. M., Pearson, T., Vincenti, F., Garcia, V. D., Campistol, J., Rial, M. C., Florman, S., Block, A., Di Russo, G., et al. (2010). A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am. J. Transplant. 10, 547-557.
10. Eastwood, D., Findlay, L., Poole, S., Bird, C., Wadhwa, M., Moore, M., Burns, C., Thorpe, R., and Stebbings, R. (2010). Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells. Br. J. Pharmacol. 161, 512-526.
11. Everly, M. J., Bloom, R. D., Tsai, D. E., and Trofe, J. (2007). Posttransplant lymphoproliferative disorder. Ann. Pharmacother. 41, 1850-1858.
12. Ferguson, S. E., Han, S., Kelsoe, G., and Thompson, C. B. (1996). CD28 is required for germinal center formation. J. Immunol. 156, 4576-4581.
13. Genovese, M. C., Becker, J. C., Schiff, M., Luggen, M., Sherrer, Y., Kremer, J., Birbara, C., Box, J., Natarajan, K., Nuamah, I., et al. (2005). Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N. Engl. J. Med. 353, 1114-1123.
14. Greenwald, R. J., Oosterwegel, M. A., van der Woude, D., Kubal, A., Mandelbrot, D. A., Boussiotis, V. A., and Sharpe, A. H. (2002). CTLA-4 regulates cell cycle progression during a primary immune response. Eur. J. Immunol. 32, 366-373.
15. Jain, S., Bicknell, G. R., and Nicholson, M. L. (2000). Tacrolimus has less fibrogenic potential than cyclosporin A in a model of renal ischaemiareperfusion injury. Br. J. Surg. 87, 1563-1568.
16. Khanna, A. K., and Pieper, G. M. (2007). NADPH oxidase subunits (NOX-1, p22phox, Rac-1) and tacrolimus-induced nephrotoxicity in a rat renal transplant model. Nephrol. Dial. Transplant. 22, 376-385.
17. Khoury, S. J., Akalin, E., Chandraker, A., Turka, L. A., Linsley, P. S., Sayegh, M. H., and Hancock, W. W. (1995). CD28-B7 costimulatory blockade by CTLA4Ig prevents actively induced experimental autoimmune encephalomyelitis and inhibits Th1 but spares Th2 cytokines in the central nervous system. J. Immunol. 155, 4521-4524.
18. Kinugasa, F., Nagatomi, I., Ishikawa, H., Nakanishi, T., Maeda, M., Hirose, J., Fukahori, H., Ooshima, S., Noto, T., Higashi, Y., et al. (2008). Efficacy of oral treatment with tacrolimus in the renal transplant model in cynomolgus monkeys. J. Pharmacol. Sci. 108, 529-534.
19. Klintmalm, G. B., and Gonwa, T. A. (1995). Nephrotoxicity associated with cyclosporine and FK506. Liver Transpl. Surg. 1, 11-19.
20. Kremer, J. M., Westhovens, R., Leon, M., Di Giorgio, E., Alten, R., Steinfeld, S., Russell, A., Dougados, M., Emery, P., Nuamah, I. F., et al. (2003). Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N. Engl. J. Med. 349, 1907-1915.
21. Krummel, M. F., and Allison, J. P. (1996). CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J. Exp. Med. 183, 2533-2540.
22. Larsen, C. P., Grinyo, J., Medina-Pestana, J., Vanrenterghem, Y., Vincenti, F., Bresnahan, B., Campistol, J. M., Florman, S., Rial, M. C., Kamar, N., et al. (2010). Belatacept-based regimens versus a cyclosporine A-based regimen in kidney transplant recipients: 2-year results from the BENEFIT and BENEFIT-EXT studies. Transplantation 90, 1528-1535.
23. Larsen, C. P., Pearson, T. C., Adams, A. B., Tso, P., Shirasugi, N., Strobert, E., Anderson, D., Cowan, S., Price, K., Naemura, J., et al. (2005). Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am. J. Transplant. 5, 443-453.
24. Lenschow, D. J., Ho, S. C., Sattar, H., Rhee, L., Gray, G., Nabavi, N., Herold, K. C., and Bluestone, J. A. (1995). Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. J. Exp. Med. 181, 1145-1155.
25. Lloberas, N., Torras, J., Alperovich, G., Cruzado, J. M., Gimenez-Bonafe, P., Herrero-Fresneda, I., Franquesa, M., Rama, I., and Grinyo, J. M. (2008). Different renal toxicity profiles in the association of cyclosporine and tacrolimus with sirolimus in rats. Nephrol. Dial. Transplant. 23, 3111-3119.
26. Meier-Kriesche, H. U., Schold, J. D., Srinivas, T. R., and Kaplan, B. (2004). Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am. J. Transplant. 4, 378-383.
27. Morales, J. M., Campistol, J. M., Andres, A., and Rodicio, J. L. (1997). Glomerular diseases in patients with hepatitis C virus infection after renal transplantation. Curr. Opin. Nephrol. Hypertens. 6, 511-515.
28. Nankivell, B. J., Borrows, R. J., Fung, C. L., O'Connell, P. J., Chapman, J. R., and Allen, R. D. (2004). Calcineurin inhibitor nephrotoxicity: Longitudinal assessment by protocol histology. Transplantation 78, 557-565.
29. Nielsen, F. T., Ottosen, P., Starklint, H., and Dieperink, H. (2003). Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat. Nephrol. Dial. Transplant. 18, 491-496.
30. Ninova, D., Covarrubias, M., Rea, D. J., Park, W. D., Grande, J. P., and Stegall, M. D. (2004). Acute nephrotoxicity of tacrolimus and sirolimus in renal isografts: Differential intragraft expression of transforming growth factor-beta1 and alpha-smooth muscle actin. Transplantation 78, 338-344.
31. Olyaei, A. J., de Mattos, A. M., and Bennett, W. M. (1999). Immunosuppressant-induced nephropathy: Pathophysiology, incidence and management. Drug Saf. 21, 471-488.
32. Pitcher, C. J., Hagen, S. I., Walker, J. M., Lum, R., Mitchell, B. L., Maino, V. C., Axthelm, M. K., and Picker, L. J. (2002). Development and homeostasis of T cell memory in rhesus macaque. J. Immunol. 168, 29-43.
33. Rezzani, R. (2004). Cyclosporine A and adverse effects on organs: Histochemical studies. Prog. Histochem. Cytochem. 39, 85-128.
34. Salomon, B., Lenschow, D. J., Rhee, L., Ashourian, N., Singh, B., Sharpe, A., and Bluestone, J. A. (2000). B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12, 431-440.
35. Shen, J., Block, A., Townsend, R., Xiaoli You, X., Shen, Y., Zhou, S., Geng, D., McGirr, N., Soucek, K., Pursley, J., et al. (2010). Pharmacokinetics, pharmacodynamics, and immunogenicity of belatacept in renal transplant patients. Transplantation 90, 426.
36. Shihab, F. S., Bennett, W. M., Tanner, A. M., and Andoh, T. F. (1997). Mechanism of fibrosis in experimental tacrolimus nephrotoxicity. Transplantation 64, 1829-1837.
37. Stillman, I. E., Andoh, T. F., Burdmann, E. A., Bennett, W. M., and Rosen, S. (1995). FK506 nephrotoxicity: morphologic and physiologic characterization of a rat model. Lab. Invest. 73, 794-803.
38. Tai, X., Cowan, M., Feigenbaum, L., and Singer, A. (2005). CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat. Immunol. 6, 152-162.
39. Takaki, A., Huang, Q. H., Somogyvari-Vigh, A., and Arimura, A. (1994). Immobilization stress may increase plasma interleukin-6 via central and peripheral catecholamines. Neuroimmunomodulation 1, 335-342.
40. Tang, Q., Henriksen, K. J., Boden, E. K., Tooley, A. J., Ye, J., Subudhi, S. K., Zheng, X. X., Strom, T. B., and Bluestone, J. A. (2003). Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J. Immunol. 171, 3348-3352.
41. Treska, V., Molacek, J., Kuntscher, V., Liska, V., Kobr, J., Racek, J., and Kormunda, S. (2004). Immunosuppresive agents have an influence on ischemia-reperfusion injury in kidneys procured from a non-heart-beating donor: Experimental study. Transplant. Proc. 36, 2931-2934.
42. Tsagarakis, S., and Grossman, A. (1994). Corticotropin-releasing hormone: Interactions with the immune system. Neuroimmunomodulation 1, 329-334.
43. Vincenti, F., Charpentier, B., Vanrenterghem, Y., Rostaing, L., Bresnahan, B., Darji, P., Massari, P., Mondragon-Ramirez, G. A., Agarwal, M., Di Russo, G., et al. (2010). A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am. J. Transplant. 10, 535-546.
44. Walunas, T. L., Bakker, C. Y., and Bluestone, J. A. (1996). CTLA-4 ligation blocks CD28-dependent T cell activation. J. Exp. Med. 183, 2541-2550.
45. Wijkstrom, M., Kirchhof, N., Graham, M., Ingulli, E., Colvin, R. B., Christians, U., Hering, B. J., and Schuurman, H. J. (2005). Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates. Toxicology 207, 117-127.