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

Andrew B. Adams, Brendan P. Lovasik, David A. Faber, Christopher Burlak, Cynthia Breeden, Jose L. Estrada, Luz M. Reyes, Rodrigo M. Vianna, Matthew F. Tector, Alfred J. Tector

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)473-480
Number of pages8
JournalAnnals of surgery
Volume274
Issue number3
DOIs
StatePublished - Sep 1 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Keywords

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

PubMed: MeSH publication types

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

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