Inactivating the Innate Immune Receptor CD11b With a First-in-Class Monoclonal Antibody Prolongs the Survival of Kidney Allografts in Nonhuman Primates.

IF 5.3 2区医学 Q1 IMMUNOLOGY

Transplantation Pub Date : 2025-03-10 DOI:10.1097/TP.0000000000005370

Abbas Dehnadi, Ivy A Rosales, Jian-Ping Xiong, Tatsuo Kawai, Hyshem H Lancia, Gilles Benichou, Robert B Colvin, A Benedict Cosimi, M Amin Arnaout

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引用次数: 0

Abstract

Backgournd: Peritransplant ischemia/reperfusion injury (IRI) plays a central pathogenic role in nondelayed or delayed kidney allograft function immediately after transplantation and increases the risk of subsequent rejection. Potential therapies targeting specific cytokines or complement proteins to limit IRI have failed in clinical trials. Monoclonal antibody 107 (mAb107), a "pure" (nonactivating) inhibitor of the archetypal innate immune receptor integrin CD11b, has been shown to extend the survival of IRI nonhuman primate native kidneys in an in situ model.

Methods: Here, we administered mAb107 before allograft revascularization to determine its efficacy for extending the survival of ischemia-damaged donor kidneys transplanted into major histocompatibility complex-mismatched nonhuman primate recipients.

Results: We observed a significant delay in the onset of rejection and prolongation of allograft survival in mAb107-treated versus control recipients. Early allograft biopsies suggest this is secondary to the selective suppression of infiltrating neutrophils and macrophages.

Conclusions: These observations support the hypothesis that inactivating CD11b with mAb107 may provide an effective strategy for prolonging the survival of ischemia-damaged allografts and increasing the successful use of marginal donor organs.

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来源期刊

Transplantation 医学-免疫学

CiteScore

8.50

自引率

11.30%

发文量

1906

审稿时长

1 months

期刊介绍： The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year. Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal. Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed. The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.