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

Abstract

The selection of possible candidate immunosuppressive antibodies to prevent graft rejection is performed in vitro. Additionally, due to the species specificity of these monoclonal antibodies (MABs), pre-clinical studies in non-human primates are necessary. If a positive correlation between the in vitro and in vivo findings would exist, these tests can act as a pre-screening before new reagents are tested in vivo. The correlation of the in vitro and 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 vivo effectiveness of ATG in rhesus monkeys. Additionally, no evidence of tolerance to a skin allograft could be shown to correlate with inhibition of a secondary mixed lymphocyte culture (MLC) by anti-CD80 and cyclosporin A (CsA). Thus, these in vitro assay used can not predict the in vivo efficacy of new immunosuppressive antibodies.