Tolerability and side effects of anti-CD3-immunotoxin in preclinical testing in kidney and pancreatic islet transplant recipients.

Academic Article

Abstract

  • 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 of nephrotoxicity 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.
  • Published In

  • Transplantation  Journal
  • Keywords

  • Animals, CD3 Complex, Capillary Leak Syndrome, Chemical and Drug Induced Liver Injury, Cyclosporine, Immune Tolerance, Immunotoxins, Islets of Langerhans Transplantation, Kidney Function Tests, Kidney Transplantation, Liver Function Tests, Macaca mulatta, Male, Methylprednisolone, Transplantation Conditioning
  • Authorlist

  • Contreras JL; Eckhoff DE; Cartner S; Frenette L; Thomas FT; Robbin ML; Neville DM; Thomas JM
  • Start Page

  • 215
  • End Page

  • 219
  • Volume

  • 68
  • Issue

  • 2