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

Adams, Andrew B., Lovasik, Brendan P., Faber, David A., Burlak, Christopher, Breeden, Cynthia, Estrada, Jose L., Reyes, Luz M., Vianna, Rodrigo M., Tector, Matthew F., Tector, Alfred J.·2021·Annals of Surgery
DOI 10.1097/sla.0000000000004996PMC PMC8915445
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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.

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Research works printed but not linked: 32

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Metadata

Authors
Adams, A. B., Lovasik, B. P., Faber, D. A., Burlak, C., Breeden, C., Estrada, J. L., Reyes, L. M., Vianna, R. M., Tector, M. F., & Tector, A. J.
Venue
Annals of Surgery
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-07-07
Volume
274
Issue
3
Pages
473-480
ISSN
  • 0003-4932
  • 1528-1140
DOI
10.1097/sla.0000000000004996
PMC
PMC8915445
Cited by
125
References
0
Language
en

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