USE OF CTLA-4IG IN COMBINATION WITH CONVENTIONAL IMMUNOSUPPRESSIVE AGENTS TO PROLONG ALLOGRAFT SURVIVAL

Background. The objective of our study was to determine the effectiven ess of CTLA4-Ig, a novel immunosuppressive agent, in augmenting allogr aft survival when combined with either cyclosporine, sirolimus, donor- specific bone marrow alone (BM), or bone marrow in conjunction with an tilymphocyte serum (ALS), Methods. 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 co mbinations of the following treatment protocols: murine CTLA4-Ig, L-6 control Ig, sirolimus, cyclosporine, ALS, or ALS/BM. Results. In the c lass I mismatch model, L-6 control Ig had no effect whereas use of CTL A4-Ig alone resulted in a doubling of the median graft survival compar ed with controls, The addition of either sirolimus or cyclosporine to CTLA4-Ig increased graft survival over that achieved with CTLA4-Ig alo ne, 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. Conclusion. These data suggest that CTLA4-Ig may be ef fective clinically in combination with cyclosporine or sirolimus but o ffers no additional effectiveness in combination with antilymphocyte s erum with or without donor-specific bone marrow.