*Purpose: Desensitization regimens have rarely been applied to deceased donor allotransplantation. We hypothesized that belatacept monotherapy during a simulated deceased donor waiting list period would improve graft survival in sensitized nonhuman primates desensitized with carfilzomib and belatacept prior to the waiting list period.

*Methods: Rhesus macaques (n=7) were sensitized to maximally MHC-mismatched donors with two sequential skin transplants, then desensitized with carfilzomib and belatacept. This was followed by a simulated waiting list period of 3 months, during which time 3 animals received belatacept monotherapy (Desensitization + Prolonged Belatacept) and 4 received no additional treatment (Desensitization Alone). Animals then received life-sustaining kidney transplants from their MHC-mismatched skin donors and received rhesus-specific antithymocyte globulin induction and standard triple immunosuppression. One animal was excluded from post-transplant analysis due to a technical complication.

*Results: Compared to animals treated with Desensitization Alone, animals treated with Desensitization + Prolonged Belatacept showed improved graft survival (p<0.05, Figure 1A), a delayed post-transplant rebound in donor-specific antibody (Figure 1B), and a more profound reduction of lymph node Tfh cells during the pre-transplant treatment period (p<0.01, Figure 1C). Tfh cells repopulated after belatacept cessation and kidney transplantation (p<0.05, not shown).

*Conclusions: Belatacept monotherapy during a simulated waitlist period was associated with improved graft survival in previously desensitized nonhuman primates and suggests a strategy for applying clinical desensitization regimens to deceased donor transplantation. Post-transplant rebound of both donor-specific antibody levels and Tfh cells suggest that alternative maintenance immunosuppression regimens that better control the germinal center response may further improve outcomes.

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