Use of in vitro correlates for selection of candidate immunosuppressive antibodies prior to a primate transplant model

The selection of possible candidate immunosuppressive antibodies to prevent graft rejection is performed in vitro. Additionally, due to the species sp ecificity of these monoclonal antibodies (MABs), pre-clinical studies in no n-human primates are necessary. If a positive correlation between the in vi tro and in vivo findings would exist, these tests can act as a prescreening before new reagents are tested in vivo. The correlation of the in vitro an d in vivo efficacy of an anti-T-lymphocyte globulin (ATG) and an anti-CD80 MAB is evaluated in a rhesus monkey skin transplant model. The results show that lymphocytotoxic titers (NIH-test) do not predict the outcome of in vi vo effectiveness of ATG in rhesus monkeys. Additionally, no evidence of tol erance to a skin allograft could be shown to correlate with inhibition of a secondary mixed lymphocyte culture (MLC) by anti-CD80 and cyclosporin A (C sA). Thus, these in vitro assay used can not predict the in vivo efficacy o f new immunosuppressive antibodies.