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

被引：75

作者：

Adams, Andrew B. ^{[1
]}

Lovasik, Brendan P. ^{[2
]}

Faber, David A. ^{[2
]}

Burlak, Christopher ^{[1
]}

Breeden, Cynthia ^{[2
]}

Estrada, Jose L. ^{[3
]}

Reyes, Luz M. ^{[3
]}

Vianna, Rodrigo M. ^{[2
]}

Tector, Matthew F. ^{[4
]}

Tector, Alfred Joseph ^{[3
]}

机构：

[1] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA

[2] Emory Sch Med, Atlanta, GA USA

[3] Univ Miami, Sch Med, Miami, FL 33136 USA

[4] Makana Therapeut, Minneapolis, MN USA

来源：

ANNALS OF SURGERY | 2021年 / 274卷 / 03期

基金：

美国国家卫生研究院;

关键词：

antibody-mediated rejection; genetically modified pigs; Kidney transplantation; tesidolumab; xenotransplantation; XENOGRAFT SURVIVAL; CELLS; PIG; ACTIVATION; TOLERANCE;

D O I：

10.1097/SLA.0000000000004996

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

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.

引用

页码：473 / 480

页数：8

共 32 条

[31] Old World Monkeys are less than ideal transplantation models for testing pig organs lacking three carbohydrate antigens (Triple-Knockout) [J].