Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates

Memory T-cells promote allograft rejection particularly in costimulation blockade (CoB)-based immunosuppressive regimens. Here we show that the CD2-specific fusion protein alefacept (LFA3-Ig) selectively eliminates memory T-cells and when combined with a CoB-based regimen utilizing CTLA4-Ig, prevents renal allograft rejection and alloantibody formation in primates. These results support the development of an immediately translatable regimen for the prevention of allograft rejection without the use of calcineurin inhibitors, steroids, or pan-T-cell depletion. Calcineurin inhibitors and glucocorticosteroids are commonly used to prevent the rejection of allografted organs; however, both agents promote many side effects (1). Blockade of the CD28/B7 costimulation pathway has been suggested as a means of preventing allograft rejection without these side effects, and indeed, the CD28/B7-specific fusion protein CTLA4-Ig has been shown to induce permanent engraftment of allografts in some rodent models, particularly when combined with the drug sirolimus and / or donor specific transfusion (DST) (2,3). Unfortunately, CTLA4-Ig with or without sirolimus is insufficient to prevent rejection in primates (reviewed in 4)