Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation.
Ann Surg
; 274(3): 473-480, 2021 09 01.
Article
em En
| MEDLINE
| ID: mdl-34238812
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 70âdays, 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 62âdays.CONCLUSION:
Inhibition of the C5 complement subunit prolongs renal xenotransplant survival in a pig to non-human primate model.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transplante Heterólogo
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Transplante de Rim
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Anticorpos Monoclonais Humanizados
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Rejeição de Enxerto
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Imunossupressores
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Anticorpos Monoclonais
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article