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

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.