Anti-C5 antibody tesidolumab reduces early antibody-mediated rejection and prolongs survival in renal xenotransplantation
AB Adams, BP Lovasik, DA Faber, C Burlak… - Annals of …, 2021 - journals.lww.com
AB Adams, BP Lovasik, DA Faber, C Burlak, C Breeden, JL Estrada, LM Reyes, RM Vianna…
Annals of surgery, 2021•journals.lww.comObjective: Pig-to-primate renal xenotransplantation is plagued by early antibody-mediated
graft loss which precludes clinical application of renal xenotransplantation. We evaluated
whether temporary complement inhibition with anti-C5 antibody Tesidolumab could
minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig
kidneys receiving costimulatory blockade-based immunosuppression. Methods: Double (Gal
and Sd a) and triple xenoantigen (Gal, Sd a, and SLA I) pigs were created using …
graft loss which precludes clinical application of renal xenotransplantation. We evaluated
whether temporary complement inhibition with anti-C5 antibody Tesidolumab could
minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig
kidneys receiving costimulatory blockade-based immunosuppression. Methods: Double (Gal
and Sd a) and triple xenoantigen (Gal, Sd a, and SLA I) pigs were created using …
Abstract
Objective:
Pig-to-primate renal xenotransplantation is plagued by early antibody-mediated graft loss which precludes clinical application of renal xenotransplantation. We evaluated whether temporary complement inhibition with anti-C5 antibody Tesidolumab could minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig kidneys receiving costimulatory blockade-based immunosuppression.
Methods:
Double (Gal and Sd a) and triple xenoantigen (Gal, Sd a, and SLA I) pigs were created using CRISPR/Cas. Kidneys from DKO and TKO pigs were transplanted into rhesus monkeys that had the least reactive crossmatches. Recipients received anti-C5 antibody weekly for 70 days, and T cell depletion, anti-CD154, mycophenolic acid, and steroids as baseline immunosuppression (n= 7). Control recipients did not receive anti-C5 therapy (n= 10).
Results:
Temporary anti-C5 therapy reduced early graft loss secondary to antibody-mediated rejection and improved graft survival (P< 0.01). Deleting class I MHC (SLA I) in donor pigs did not ameliorate early antibody-mediated rejection (table). Anti-C5 therapy did not allow for the use of tacrolimus instead of anti-CD154 (table), prolonging survival to a maximum of 62 days.
Conclusion:
Inhibition of the C5 complement subunit prolongs renal xenotransplant survival in a pig to non-human primate model.
Lippincott Williams & Wilkins