The road to tolerance: renal transplant tolerance induction in nonhuman primate studies and clinical trials.
Organ transplantation has become a standard life-saving therapy for many causes of end stage organ failure. Although valuable, it remains hampered by the requirement for, and complications of, immunosuppression to prevent immune rejection of the transplanted organ. It is now clear that rejection can be avoided in some experimental systems without a requirement of immunosuppressive medication, and these experimental concepts are now making their way into the clinic in the form of early transplantation tolerance trials. This manuscript will discuss the most promising techniques for tolerance induction, namely, costimulation blockade, lymphocyte depletion, and mixed chimerism. Seminal preclinical studies will be cited and the results of initial clinical trials will be reviewed. The data to date indicate that while tolerance remains elusive, immunosuppression minimization is a feasible near-term alternative.
Elster
Eric A
EA
Department of Health and Human Services, Transplantation Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hale
Douglas A
DA
Mannon
Roslyn B
RB
Cendales
Linda C
LC
Swanson
S John
SJ
Kirk
Allan D
AD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002986:Clinical Trials as Topic; D017635:Clonal Anergy; D005544:Forecasting; D006084:Graft Rejection / Q000517:prevention & control; D000882:Haplorhini; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D018448:Models, Immunological; D010215:Papio; D011323:Primates; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007166:Immunosuppressive Agents; D023201:CD40 Ligand