Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation

Ann Surg. 2021 Sep 1;274(3):473-480. doi: 10.1097/SLA.0000000000004996.


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 Sda) and triple xenoantigen (Gal, Sda, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antibiotic Prophylaxis
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control*
  • Immune Tolerance
  • Immunosuppressive Agents / pharmacology*
  • Kidney Transplantation*
  • Macaca mulatta
  • Models, Animal
  • Rituximab / pharmacology
  • Swine
  • Tacrolimus / pharmacology
  • Transplantation, Heterologous*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunosuppressive Agents
  • tesidolumab
  • Rituximab
  • Tacrolimus