I’ve been interested in the potential of Alefacept in renal transplant for a while. So far it appears to have a favorable side effect profile (no PML last I checked) and it’s also injectable which makes it more convenient (though increases risk of non-compliance vs IV).
Biologics in general are attractive due to increased specificity and the promise of fewer adverse effects, but that increased specificity also means something may slip through the immunosuppressive net, as shown in the first article. The inconsistent results in these studies are likely a reflection of that effect, and selecting the right combinations of agents will become even more important as specificity increases. The concern in combining a number of specific agents to avoid graft failure is that the risks of oversuppression will be increased significantly. Until immune responses specific to the donated organ can be targeted that trade-off will always be a limiting factor for long-term outcomes.
As always, if reading about immunosuppressants doesn’t leave you feeling hopeless and confused you clearly missed something….
Selective targeting of human alloresponsive CD8+ effector memory T-cells. Benefits of combining Belatacept and Alefacept. Also brings up the concerns with wiping the memory of the immune system. Could also explain why this primate trial was successful.
On the other hand this islet transplant study showed no benefit to adding Alefacept to Belatacept-SRL.
Amevive/Alefacept FDA briefing document.
Because Alefacept is only beginning to be studied in transplantation here are a few related studies and reviews: