Use of CTLA4-Ig in combination with conventional immunosuppressive agents to prolong allograft survival

• Published in: Transplantation Vol. 64; no. 6; p. 897
• Main Authors: Hale, D A, Gottschalk, R, Maki, T, Monaco, A P
• Format: Journal Article
• Language: English
• Published: United States 27.09.1997
• Subjects: Abatacept; Animals; Antigens, CD; Antigens, Differentiation - therapeutic use; Antilymphocyte Serum - therapeutic use; Bone Marrow Transplantation - immunology; CTLA-4 Antigen; Cyclosporine - therapeutic use; Drug Therapy, Combination; Graft Survival - drug effects; Graft Survival - immunology; Histocompatibility Testing; Immunization, Passive; Immunoconjugates; Immunosuppression - methods; Immunosuppressive Agents - therapeutic use; Mice; Mice, Inbred AKR; Mice, Inbred C3H; Mice, Inbred C57BL; Polyenes - therapeutic use; Sirolimus; Skin Transplantation - immunology; Transplantation, Homologous
• ISSN: 0041-1337
• DOI: 10.1097/00007890-199709270-00018

The objective of our study was to determine the effectiveness of CTLA4-Ig, a novel immunosuppressive agent, in augmenting allograft survival when combined with either cyclosporine, sirolimus, donor-specific bone marrow alone (BM), or bone marrow in conjunction with antilymphocyte serum (ALS). Full-thickness skin allografts were used in C3H to B6AF1 (class I mismatch) and AKR to C57BL/6 (complete mismatch) models. Groups of mice (n=6-14) were treated with various combinations of the following treatment protocols: murine CTLA4-Ig, L-6 control Ig, sirolimus, cyclosporine, ALS, or ALS/BM. In the class I mismatch model, L-6 control Ig had no effect whereas use of CTLA4-Ig alone resulted in a doubling of the median graft survival compared with controls. The addition of either sirolimus or cyclosporine to CTLA4-Ig increased graft survival over that achieved with CTLA4-Ig alone. CTLA4-Ig demonstrated no efficacy when used in combination with BM, ALS, or ALS/BM. CTLA4-Ig was clearly less effective in the complete mismatch model. These data suggest that CTLA4-Ig may be effective clinically in combination with cyclosporine or sirolimus but offers no additional effectiveness in combination with antilymphocyte serum with or without donor-specific bone marrow.