Effects of humanized monoclonal antibody to rhesus CD11a in rhesus monkey cardiac allograft recipients

Robert S. Poston, Robert C. Robbins, Betty Chan, Paul Simms, Len Presta, Paula Jardieu, Randall E. Morris

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Introduction. Leukocyte function-associated antigen-1 (LFA-1, CD11a) monoclonal antibody (mAb) affects many leukocyte functions without cell depletion. We hypothesized that the use of a humanized, antirhesus modified LFA-1 mAb (H2C12) in rhesus monkeys would cause: (1) prolonged heart allograft survival, (2) inhibition of primary but not secondary antibody responses, and (3) minimal drug toxicity. Methods and Results. Control (n=5) and H2C12-treated (n=7) (8-20 mg/kg i.v. on day -1 followed by 10 mg/kg/day) adult male rhesus recipients were inoculated with GP120 protein antigen on day -28 and -1 and grafted with heterotopic abdominal hearts (day 0). Donor- recipient pairs were equally MLR mismatched (4329±81124.1 CPM controls vs. 7289.0±1926.5 treated, P=NS). Mean heart allograft survival as evaluated by daily abdominal palpation was significantly prolonged in high dose recipients (23.02±2.6, n=4) versus controls (8.2±1.3, n=5, P<0.02, Mann-Whitney U test). H2C12 treatment did not produce signs of cytokine release or toxicity, was nondepleting, but down-modulated PBL CD11a expression to 43.4±3.6% (n=4) of control levels (n=5) at day 7 as demonstrated by flow cytometry. It had no effect on postoperative Con A or MLR and did not prevent mAb clearance due to the rhesus-antihuman antibody response. The addition of mycophenolate mofitil prevented rhesus-antihuman antibody response with therapeutic H2C12 levels seen for >35 days. Conclusions. The use of this mAb to block CD11a had the benefit of being a well tolerated, highly targeted therapy. These are the first results showing that monotherapy with anti-leukocyte function- associated antigen-1 mAb prolonged survival of MLR mismatched allogenic cardiac grafts in primates.

Original languageEnglish (US)
Pages (from-to)2005-2013
Number of pages9
Issue number10
StatePublished - May 27 2000
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation


Dive into the research topics of 'Effects of humanized monoclonal antibody to rhesus CD11a in rhesus monkey cardiac allograft recipients'. Together they form a unique fingerprint.

Cite this