vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2013-1-96-105vtio-146Research ArticleОбзор литературыLiterature ReviewsБЕЛАТАЦЕПТ ПРИ ТРАНСПЛАНТАЦИИ ПОЧКИBELATACEPT IN RENAL TRANSPLANTATIONСушковА. И.SushkovA. I.МойсюкЯ. Г.MoysyukY. G.ФГБУ «Федеральный научный центр трансплантологии и искусственных органов им. академика В.И. Шумакова» Минздрава РФ, г. МоскваAcademician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, MoscowФГБУ «Федеральный научный центр трансплантологии и искусственных органов им. академика В.И. Шумакова» Минздрава РФ, г. Москва ГБОУ ВПО «Первый МГМУ им. И.М. Сеченова», кафедра трансплантологии и искусственных органовAcademician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, Moscow I.M. Sechenov First Moscow State Medical University, Department of Transplantology and Artificial Organs, Moscow201327052014151ВЕСТНИК ТРАНСПЛАНТОЛОГИИ И ИСКУССТВЕННЫХ ОРГАНОВ том XV No 1–201396105Copyright © Сушков А.И., Мойсюк Я.Г., 20132013Сушков А.И., Мойсюк Я.Г.Sushkov A.I., Moysyuk Y.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/146

Белатацепт – новый иммунодепрессант, подавляющий активацию T-лимфоцитов за счет блокады ко- стимулирующей молекулы CD28. Белатацепт был разработан на основе абатацепта (CTLA-4 Ig) – реком- бинантного иммуноглобулина, который состоит из внеклеточной части молекулы CTLA-4 и константного домена IgG. Первые клинические исследования показали, что при сравнимых результатах выживаемости пациентов и трансплантатов скорость клубочковой фильтрации в группе пациентов, получавших белата- цепт, была выше, чем в группе получавших циклоспорин А. Биологические иммуносупрессивные пре- параты представляют значительный интерес в первую очередь из-за того, что не обладают присущими ингибиторам кальциневрина (ИКН) побочными действиями. Белатацепт, возможно, может стать альтер- нативой ИКН в схемах поддерживающей иммуносупрессивной терапии после трансплантации почки. Однако большая частота эпизодов острого клеточного отторжения и повышенный риск развития пост- трансплантационных лимфопролиферативных заболеваний (ПТЛЗ) вызывают настороженность и требу- ют продолжения клинических исследований препарата. 

Belatacept is a novel immunosuppressive agent that inhibits T-cell activation by blocking CD28 signaling pa- thway. It was developed based on abatacept (CTLA-4Ig), the first recombinant immunoglobulin fusion protein which contains extracellular part of CTLA-4 molecule and Fc domain of IgG. First clinical trials have shown the comparable patient and graft survival in group of kidney recipients with belatacept-based maintenance im- munosuppressive therapy versus Cyclosporin A-based therapy. Advantages observed with belatacept include superior glomerular filtration rate and improved cardiovascular risk profile. Belatacept is a potential option for maintenance immunosuppressive therapy without calcineurin inhibitors. Concerns associated with belatacept use are higher rates of acute cellular rejection episodes and post-transplant lymphoproliferative disorder cases. 

трансплантация почкибелатацептCTLA-4 IgCD28kidney transplantationbelataceptCTLA-4 IgCD28ReferencesМойсюк Я.Г. и соавт. Иммуносупрессия при транс- плантации почки // Иммуносупрессия при транс- плантации солидных органов / Под ред. С.В. Готье. М.: Триада, 2011. С. 46–113.Мойсюк Я.Г. и соавт. Иммуносупрессия при транс- плантации почки // Иммуносупрессия при транс- плантации солидных органов / Под ред. С.В. Готье. М.: Триада, 2011. С. 46–113.Abrams J.R. et al. Blockade of T lymphocyte costimu- lation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pa- thology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells // J. Exp. Med. 2000. Vol. 192 (5). P. 681–694.Abrams J.R. et al. Blockade of T lymphocyte costimu- lation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pa- thology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells // J. Exp. Med. 2000. Vol. 192 (5). P. 681–694.Adams A.B. et al. Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival // J. Immunol. 2005. Vol. 174 (1). P. 542–550.Adams A.B. et al. Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival // J. Immunol. 2005. Vol. 174 (1). P. 542–550.Cardona K. et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways // Nat. Med. 2006. Vol. 12 (3). P. 304–306.Cardona K. et al. Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways // Nat. Med. 2006. Vol. 12 (3). P. 304–306.Davis P.M., Nadler S. and Suchard S.J. Belatacept does not mediate complement-dependent cytotoxicity or an- tibody-dependent cellular cytotoxicity // Am. J. Trans- plant. 2008. Vol. 8.Davis P.M., Nadler S. and Suchard S.J. Belatacept does not mediate complement-dependent cytotoxicity or an- tibody-dependent cellular cytotoxicity // Am. J. Trans- plant. 2008. Vol. 8.Durrbach A., Grinyo J. and Vanrenterghem Y. Bela- tacept compared with cyclosporine in renal allograft recipients of extended criteria donor kidneys: 3-year outcomes from the phase III BENEFIT-EXT trial, in Annual Congress ERA EDTA. 2011: Prague, Czech Republic.Durrbach A., Grinyo J. and Vanrenterghem Y. Bela- tacept compared with cyclosporine in renal allograft recipients of extended criteria donor kidneys: 3-year outcomes from the phase III BENEFIT-EXT trial, in Annual Congress ERA EDTA. 2011: Prague, Czech Republic.Durrbach A. et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended crite- ria donors (BENEFIT-EXT study) // Am. J. Transplant. 2010. Vol. 10 (3). P. 547–557.Durrbach A. et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended crite- ria donors (BENEFIT-EXT study) // Am. J. Transplant. 2010. Vol. 10 (3). P. 547–557.Emamaullee J.A. et al. Belatacept and basiliximab di- minish human antiporcine xenoreactivity and synergize to inhibit alloimmunity // Transplantation. 2008. Vol. 85 (1). P. 118–124.Emamaullee J.A. et al. Belatacept and basiliximab di- minish human antiporcine xenoreactivity and synergize to inhibit alloimmunity // Transplantation. 2008. Vol. 85 (1). P. 118–124.Ferguson R. et al. Immunosuppression with belatacept- based, corticosteroid-avoiding regimens in de novo kidney transplant recipients // Am. J. Transplant. 2011. Vol. 11 (1). P. 66–76.Ferguson R. et al. Immunosuppression with belatacept- based, corticosteroid-avoiding regimens in de novo kidney transplant recipients // Am. J. Transplant. 2011. Vol. 11 (1). P. 66–76.Fife B.T., Bluestone J.A. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways // Immunol. Rev. 2008. Vol. 224. P. 166–182.Fife B.T., Bluestone J.A. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways // Immunol. Rev. 2008. Vol. 224. P. 166–182.Gaston R.S. Chronic calcineurin inhibitor nephrotoxici- ty: reflections on an evolving paradigm // Clin. J. Am. Soc. Nephrol. 2009. Vol. 4 (12). P. 2029–2034.Gaston R.S. Chronic calcineurin inhibitor nephrotoxici- ty: reflections on an evolving paradigm // Clin. J. Am. Soc. Nephrol. 2009. Vol. 4 (12). P. 2029–2034.Grinyo J. et al. An integrated safety profile analysis of belatacept in kidney transplant recipients // Transplanta- tion. 2010. Vol. 90 (12). P. 1521–1527.Grinyo J. et al. An integrated safety profile analysis of belatacept in kidney transplant recipients // Transplanta- tion. 2010. Vol. 90 (12). P. 1521–1527.Hess R.D. Routine Epstein–Barr virus diagnostics from the laboratory perspective: still challenging after 35 ye- ars // J. Clin. Microbiol. 2004. Vol. 42 (8). P. 3381–3387.Hess R.D. Routine Epstein–Barr virus diagnostics from the laboratory perspective: still challenging after 35 ye- ars // J. Clin. Microbiol. 2004. Vol. 42 (8). P. 3381–3387.Kirk A.D. et al. Induction therapy with monoclonal anti- bodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates // Transplantation, 2001. Vol. 72 (3). P. 377–384.Kirk A.D. et al. Induction therapy with monoclonal anti- bodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates // Transplantation, 2001. Vol. 72 (3). P. 377–384.Kremer J.M. et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion pro- tein CTLA4Ig // N. Engl. J. Med. 2003. Vol. 349 (20). P. 1907–1915.Kremer J.M. et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion pro- tein CTLA4Ig // N. Engl. J. Med. 2003. Vol. 349 (20). P. 1907–1915.Larsen C.P. et al. Rational development of LEA29Y (be- latacept), a high-affinity variant of CTLA4-Ig with po- tent immunosuppressive properties // Am. J. Transplant. 2005. Vol. 5 (3). P. 443–453.Larsen C.P. et al. Rational development of LEA29Y (be- latacept), a high-affinity variant of CTLA4-Ig with po- tent immunosuppressive properties // Am. J. Transplant. 2005. Vol. 5 (3). P. 443–453.Latek R. et al. Assessment of belatacept-mediated co- stimulation blockade through evaluation of CD80/86- receptor saturation // Transplantation. 2009. Vol. 87 (6). P. 926–933.Latek R. et al. Assessment of belatacept-mediated co- stimulation blockade through evaluation of CD80/86- receptor saturation // Transplantation. 2009. Vol. 87 (6). P. 926–933.Levisetti M.G. et al. Immunosuppressive effects of hu- man CTLA4Ig in a non-human primate model of allo- geneic pancreatic islet transplantation // J. Immunol. 1997. Vol. 159 (11). P. 5187–5191.Levisetti M.G. et al. Immunosuppressive effects of hu- man CTLA4Ig in a non-human primate model of allo- geneic pancreatic islet transplantation // J. Immunol. 1997. Vol. 159 (11). P. 5187–5191.Li X.C., Rothstein D.M., Sayegh M.H. Costimulatory pa- thways in transplantation: challenges and new develop- ments // Immunol. Rev. 2009. Vol. 229 (1). P. 271–293.Li X.C., Rothstein D.M., Sayegh M.H. Costimulatory pa- thways in transplantation: challenges and new develop- ments // Immunol. Rev. 2009. Vol. 229 (1). P. 271–293.Linsley P.S. et al. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors // Immunity. 1994. Vol. 1 (9). P. 793–801.Linsley P.S. et al. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors // Immunity. 1994. Vol. 1 (9). P. 793–801.Linsley P.S. et al. Immunosuppression in vivo by a so- luble form of the CTLA-4 T cell activation molecule // Science. 1992. Vol. 257 (5071). P. 792–795.Linsley P.S. et al. Immunosuppression in vivo by a so- luble form of the CTLA-4 T cell activation molecule // Science. 1992. Vol. 257 (5071). P. 792–795.Meier-Kriesche H.U., Schold J.D., Kaplan B. Long- term renal allograft survival: have we made significant progress or is it time to rethink our analytic and thera- peutic strategies? // Am. J. Transplant. 2004. Vol. 4 (8). P. 1289–1295.Meier-Kriesche H.U., Schold J.D., Kaplan B. Long- term renal allograft survival: have we made significant progress or is it time to rethink our analytic and thera- peutic strategies? // Am. J. Transplant. 2004. Vol. 4 (8). P. 1289–1295.Nankivell B.J. et al. The natural history of chronic al- lograft nephropathy // N. Engl. J. Med. 2003. Vol. 349 (24). P. 2326–2333.Nankivell B.J. et al. The natural history of chronic al- lograft nephropathy // N. Engl. J. Med. 2003. Vol. 349 (24). P. 2326–2333.Rangel E.B. Belatacept in clinical and experimental transplantation – progress and promise // Drugs Today (Barc). 2010. Vol. 46 (4). P. 235–242.Rangel E.B. Belatacept in clinical and experimental transplantation – progress and promise // Drugs Today (Barc). 2010. Vol. 46 (4). P. 235–242.Sakaguchi S. et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and trans- plantation tolerance // Immunol. Rev. 2001. Vol. 182. P. 18–32.Sakaguchi S. et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and trans- plantation tolerance // Immunol. Rev. 2001. Vol. 182. P. 18–32.Tang, Q. et al. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells // J. Im- munol. 2003. Vol. 171 (7). P. 3348–3352.Tang, Q. et al. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells // J. Im- munol. 2003. Vol. 171 (7). P. 3348–3352.Vanrenterghem Y. et al. Belatacept-based regimens are associated with improved cardiovascular and metabolic risk factors compared with cyclosporine in kidney transplant recipients (BENEFIT and BENEFIT-EXT studies) // Transplantation. 2011. Vol. 91 (9). P. 976–983.Vanrenterghem Y. et al. Belatacept-based regimens are associated with improved cardiovascular and metabolic risk factors compared with cyclosporine in kidney transplant recipients (BENEFIT and BENEFIT-EXT studies) // Transplantation. 2011. Vol. 91 (9). P. 976–983.Vierboom M.P. et al. Induction of allograft tolerance through costimulatory blockade: first selection of drugs in vitro // Transpl. Immunol. 2003. Vol. 11 (2). P. 215– 222.Vierboom M.P. et al. Induction of allograft tolerance through costimulatory blockade: first selection of drugs in vitro // Transpl. Immunol. 2003. Vol. 11 (2). P. 215– 222.Vincenti F. et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine inVincenti F. et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine inrenal transplant recipients (BENEFIT study) // Am. J.renal transplant recipients (BENEFIT study) // Am. J.Transplant. 2010. Vol. 10 (3). P. 535–546.Transplant. 2010. Vol. 10 (3). P. 535–546.Vincenti F., Larsen C., Alberu J. Three-year outcomes from benefit: a phase III study of belatacept vs. cyclospo- rine in kidney transplant recipients., in Annual CongressVincenti F., Larsen C., Alberu J. Three-year outcomes from benefit: a phase III study of belatacept vs. cyclospo- rine in kidney transplant recipients., in Annual CongressERA EDTA. 2011: Prague, Czech Republic.ERA EDTA. 2011: Prague, Czech Republic.Vincenti F. et al. Costimulation blockade with belatacept in renal transplantation // N. Engl. J. Med. 2005. Vol. 353Vincenti F. et al. Costimulation blockade with belatacept in renal transplantation // N. Engl. J. Med. 2005. Vol. 353(8). P. 770–781.(8). P. 770–781.

The authors declare that there are no conflicts of interest present.