Tolerability and side effects of anti-CD3-immunotoxin in preclinical testing in kidney and pancreatic islet transplant recipients
Contreras, J.L.; Eckhoff, D.E.; Cartner, S.; Frenette, L.; Thomas, F.T.; Robbin, M.L.; Neville, D.M.; Thomas, J.M.
Transplantation 68(2): 215-219
1999
ISSN/ISBN: 0041-1337 PMID: 10440390 Document Number: 508482
Introduction. Anti-CD3-immunotoxin (alpha-CD3-IT) promotes allograft tolerance in nonhuman primates owing to efficient depletion of sessile and circulating T cells. Common side effects of vascular leak syndrome, hepatotoxicity, and nephrotoxicity have limited tolerability of other immunotoxins. We report on preclinical studies of alpha-CD3-IT-related side effects. Methods. Normal rhesus monkeys received a kidney transplant and alpha-CD3-IT alone (on day -to +2) or in combination with brief peritransplant adjunctive immunosuppressive therapy. Some received donor CD34+ cells. Blood chemistries, complete blood count, weight, liver, and kidney biopsies were examined for immunotoxin-related changes. Five spontaneously diabetic primates also received alpha-CD3-IT, three of whom had a pancreas islet transplant. Results. The main side effect of alpha-CD3-IT, vascular leak syndrome, was entirely prevented by adjunctive immunosuppressive therapy. Renal and liver function tests and biopsies revealed a lack ofnephrotoxicity and hepatotoxicity. All had transient weight loss (14 +- 5%). Without infusion of donor CD34+ cells, 97% had full weight recovery. Of those given donor CD34+ cells, 50% were euthanized for wasting. Conclusions. Side effects of alpha-CD3-IT are manageable and should not prevent therapeutic application.