CD40-CD40L Blockade: Update on Novel Investigational Therapeutics for Transplantation

Overview

Journal Transplantation

Specialty General Surgery

Date 2022 Dec 30

PMID 36584382

Authors

Avneesh K Singh

Corbin E Goerlich

Tianshu Zhang

Billeta G T Lewis

Alena Hershfeld

Muhammad M Mohiuddin

Affiliations

Soon will be listed here.

Abstract

Effective immune responses require antigen presentation by major histocompatibility complexes with cognate T-cell receptor and antigen-independent costimulatory signaling for T-cell activation, proliferation, and differentiation. Among several costimulatory signals, CD40-CD40L is of special interest to the transplantation community because it plays a vital role in controlling or regulating humoral and cellular immunity. Blockade of this pathway has demonstrated inhibition of donor-reactive T-cell responses and prolonged the survival of transplanted organs. Several anti-CD154 and anti-CD40 antibodies have been used in the transplantation model and demonstrated the potential of extending allograft and xenograft rejection-free survival. The wide use of anti-CD154 antibodies was hampered because of thromboembolic complications in transplant recipients. These antibodies have been modified to overcome the thromboembolic complications by altering the antibody binding fragment (Fab) and Fc (fragment, crystallizable) receptor region for therapeutic purposes. Here, we review recent preclinical advances to target the CD40-CD40L pair in transplantation.

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