1. Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates.
- Author
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Weaver TA, Charafeddine AH, Agarwal A, Turner AP, Russell M, Leopardi FV, Kampen RL, Stempora L, Song M, Larsen CP, and Kirk AD
- Subjects
- Abatacept, Alefacept, Animals, Blood Transfusion, CD2 Antigens analysis, Immunoconjugates pharmacology, Immunologic Memory, Macaca mulatta, Sirolimus pharmacology, T-Lymphocytes immunology, Transplantation, Homologous, Graft Survival drug effects, Kidney Transplantation, Recombinant Fusion Proteins pharmacology
- Abstract
Memory T cells promote allograft rejection particularly in co-stimulation blockade-based immunosuppressive regimens. Here we show that the CD2-specific fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig) selectively eliminates memory T cells and, when combined with a co-stimulation blockade-based regimen using cytotoxic T lymphocyte antigen-4 (CTLA-4)-Ig, a CD80- and CD86-specific fusion protein, prevents renal allograft rejection and alloantibody formation in nonhuman primates. These results support the immediate translation of a regimen for the prevention of allograft rejection without the use of calcineurin inhibitors, steroids or pan-T cell depletion.
- Published
- 2009
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