A Phase I/II Randomized Open-Label Multicenter Trial of Efalizumab, a Humanized Anti-CD11a, Anti-LFA-1 in Renal Transplantation
Authors: Vincenti, F.; Mendez, R.1; Pescovitz, M.2; Rajagopalan, P. R.3; Wilkinson, A. H.4; Butt, K.5; Laskow, D.6; Slakey, D. P.7; Lorber, M. I.8; Garg, J. P.9; Garovoy, M.10
Source: American Journal of Transplantation, Volume 7, Number 7, July 2007 , pp. 1770-1777(8)
Publisher: Blackwell Publishing
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Abstract:
Leukocyte function associated antigen-1 (LFA-1) has a multifaceted role in the immune response, including adhesion and trafficking of leukocytes, stabilizing the immune synapse of the MHC-TCR complex and providing costimulation signals. Monoclonal antibodies to the CD11a chain of LFA-1 have been seen to result in effective immunosuppression in experimental models. Efalizumab, a humanized IgG1 anti-CD11a, is approved for use in psoriasis and may provide effective immunosuppression in organ transplantation. Thirty-eight patients undergoing their first living donor or deceased renal transplant were randomized to receive efalizumab 0.5 or 2 mg/kg weekly subcutaneously for 12 weeks. Patients were maintained on full dose cyclosporine, mycophenolate mofetil and steroids or half dose cyclosporine, sirolimus and prednisone. At 6 months following transplant patient survival was 97% and graft survival was 95%. Clinical biopsy-proven acute rejection in the first 6 months after transplantation was confirmed in 4 of 38 patients (11%). Three patients (8%) developed post transplant lymphoproliferative disease, all treated with the higher dose efalizumab and full dose cyclosporine. The two doses of efalizumab resulted in comparable saturation and modulation of CD11a. This phase II trial suggests that efalizumab may warrant further investigation in transplantation.Keywords: Adhesion molecules; anti-LFA; efalizumab; induction; monoclonal antibodies; renal transplantation
Document Type: Research article
DOI: 10.1111/j.1600-6143.2007.01845.x
Affiliations: 1: National Institute of Transplantation; Los Angeles, CA 2: Department of Surgery, Microbiology/Immunology, Indiana University, Indianapolis, IN 3: Division of Transplant Surgery, Medical University of South Carolina, Charleston, SC 4: David Geffen School of Medicine at UCLA, Nephrology Division, Kidney and Pancreas Transplantation, Valhalla, NY 5: Department of Transplant Surgery, Westchester Medical Center, Valhalla, NY 6: Department of Pediatric Nephrology and Transplant Surgery, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 7: Tulane Center for Abdominal Transplant, Tulane University Health Sciences Center, New Orleans, LA 8: Section of Organ Transplantation and Immunology, Yale University School of Medicine, New Haven, CT 9: ITGR, Genentech, Inc, South San Francisco, CA 10: XOMA (US) LLC, Berkeley, CA
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