ALTEX :: Alternatives to Animal Experiments

1998, Supplement

Use of In Vitro Correlates for Selection of Candidate Immunosuppressive Antibodies Prior to a Primate Transplant Model

Miriam A. Ossevoort¹, Maria C. Noort¹, Almuth Radzikowski², Yvon Van Der Hout¹, Katrien Lorré³, Peter De Waele³, and Margreet Jonker¹

¹Dept. of Immunotherapy, Biomedical Primate Research Centre, NL-Rijswijk; ²Fresenius AG, D-Gräfelfing; ³Innogenetics NV, B-Gent

SUMMARY

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), preclinical studies in nonhuman primates are necessary. If a positive correlation between the in vitro 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 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 assays used cannot predict the in vivo efficacy of new immunosuppressive antibodies.

Keywords: transplantation, antibodies, in vitro, primates