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 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.
Ossevoort
Miriam A.
MA
Dept. of Immunotherapy, Biomedical Primate Research Centre, NL-Rijswijk.
Noort
Maria C.
MC
Radzikowski
Almuth
A
Lorré
Katrien
K
De Waele
Peter
P
Jonker
Margreet
M