Short course single agent therapy with an LFA-3-IgG1 fusion protein prolongs primate cardiac allograft survival

Richard J. Kaplon, Paula S. Hochman, Robert E. Michler, Pawel A. Kwiatkowski, Niloo M. Edwards, Carole L. Berger, H. E. Xu, Werner Meier, Barbara P. Wallner, Patricia Chisholm, Charles C. Marboe

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The interaction of T cell costimulatory molecules with their ligands is required for optimal T cell activation. Interference with such interactions can induce antigen unresponsiveness and delay xeno- and allograft rejection. We have previously shown that LFA3TIP, a soluble human lymphocyte function- associated antigen (LFA)-3 construct, binds CD2 and inhibits responses of human T cell in vitro. This study reports the first use of a human fusion protein, LFA3TIP, to significantly prolong primate cardiac allograft survival. Based on our observation that LFA3TIP inhibits baboon allogeneic mixed lymphocyte reactions, we gave baboon recipients of heterotopic cardiac allografts injections of LFA3TIP, 3 mg/kg i.v., for 12 consecutive days, starting 2 days before transplantation. This regimen delayed graft rejection from an average of 10.6±2.3 days for human IgG-treated controls (n=5) to an average of 18.0±5.3 days for LFA3TIP-injected animals (n=7; P≤0.01). Grafts from LFA3TIP-treated animals showed markedly diminished coronary endothelialitis as compared with control animals. LFA3TIP reached peak serum levels of approximately 100 μg/ml after 7-9 injections and persisted in the 10-μg/ml range for 1 to 2 weeks after the final injection. Despite these blood levels, circulating antibodies to LFA3TIP were not detected in the serum. No renal or hepatic toxicity was noted. The possible mechanism by which LFA3TIP acts to inhibit graft rejection is discussed; success in prolonging graft survival when LFA3TIP is used as a single-agent therapy suggests great potential for this novel therapeutic agent.

Original languageEnglish (US)
Pages (from-to)356-363
Number of pages8
JournalTransplantation
Volume61
Issue number3
DOIs
StatePublished - Feb 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Short course single agent therapy with an LFA-3-IgG<sub>1</sub> fusion protein prolongs primate cardiac allograft survival'. Together they form a unique fingerprint.

  • Cite this

    Kaplon, R. J., Hochman, P. S., Michler, R. E., Kwiatkowski, P. A., Edwards, N. M., Berger, C. L., Xu, H. E., Meier, W., Wallner, B. P., Chisholm, P., & Marboe, C. C. (1996). Short course single agent therapy with an LFA-3-IgG1 fusion protein prolongs primate cardiac allograft survival. Transplantation, 61(3), 356-363. https://doi.org/10.1097/00007890-199602150-00004