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.
journal_name
Transplantationjournal_title
Transplantationauthors
Contreras JL,Eckhoff DE,Cartner S,Frenette L,Thomas FT,Robbin ML,Neville DM Jr,Thomas JMdoi
10.1097/00007890-199907270-00009subject
Has Abstractpub_date
1999-07-27 00:00:00pages
215-9issue
2eissn
0041-1337issn
1534-6080journal_volume
68pub_type
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