Treatment with the humanized CD154-specific monoclonal antibody, hu5C8, prevents acute rejection of primary skin allografts in nonhuman primates.
Published
Journal Article
BACKGROUND: Allogeneic skin transplantation remains a rigorous test of any immune intervention designed to prevent allograft rejection. To date, no single, clinically available immunosuppressant has been reported to induce long-term primary skin allograft survival in primates. We have previously shown that treatment with the humanized CD154-specific monoclonal antibody, humanized 5C8 (hu5C8), induces long-term renal allograft survival in nonhuman primates. In this study, we evaluated the efficacy of hu5C8 in preventing primary skin allograft rejection in rhesus monkeys. METHODS: Ten rhesus monkeys were transplanted with full-thickness skin allografts mismatched at both class I and class II major histocompatibility loci. Of these, two were given no treatment, five were treated with hu5C8 alone, and three received hu5C8 combined with whole blood donor-specific transfusion (DST). All recipients also received skin autografts for comparison. Animals were followed by inspection, serial biopsy, mixed lymphocyte culture, and alloantibody determination. RESULTS: Treatment with hu5C8 alone or hu5C8 plus DST greatly prolonged allograft survival. Rejection occurred in the untreated group within 7 days. Mean allograft survival in the monotherapy hu5C8 group was >236 days and in the DST group was >202 days; these differences were not significant. Rejection eventually occurred in most animals. Allograft survival was not correlated with the development of T cell hyporesponsiveness in mixed lymphocyte culture. Rejection was not predicted by the development of donor-specific alloantibody. CONCLUSION: These results show that treatment with the CD154-specific monoclonal antibody, hu5C8, greatly delays the onset of acute skin allograft rejection.
Full Text
Duke Authors
Cited Authors
- Elster, EA; Xu, H; Tadaki, DK; Montgomery, S; Burkly, LC; Berning, JD; Baumgartner, RE; Cruzata, F; Marx, R; Harlan, DM; Kirk, AD
Published Date
- November 15, 2001
Published In
Volume / Issue
- 72 / 9
Start / End Page
- 1473 - 1478
PubMed ID
- 11707732
Pubmed Central ID
- 11707732
International Standard Serial Number (ISSN)
- 0041-1337
Digital Object Identifier (DOI)
- 10.1097/00007890-200111150-00001
Language
- eng
Conference Location
- United States