Novel insights into anti-CD40/CD154 immunotherapy in transplant tolerance

• Type of Material: Article
• Authors: David F. Pinelli, Emory University; Mandy Ford, Emory University
• Language: English
• Date: 2015-01-01
• Publisher: Future Medicine
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Future Medicine Ltd
• Final Published Version (URL): http://dx.doi.org/10.2217/IMT.15.1
• Title of Journal or Parent Work: Immunotherapy
• ISSN: 1750-743X
• Volume: 7
• Issue: 4
• Start Page: 399
• End Page: 410
• Keywords: Life Sciences & Biomedicine; IN-VIVO; REGULATORY T-CELLS; CD40; ISLET ALLOGRAFT SURVIVAL; DENDRITIC CELLS; CD40L; transplantation; CUTTING EDGE; CD40 LIGAND; KIDNEY-TRANSPLANTATION; ANTI-CD154 MONOCLONAL-ANTIBODY; NONHUMAN-PRIMATES; costimulation; COSTIMULATION BLOCKADE; thromboembolism; Fc receptor; Science & Technology; Immunology
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery

Abstract

Since the discovery of the CD40-CD154 costimulatory pathway and its critical role in the adaptive immune response, there has been considerable interest in therapeutically targeting this interaction with monoclonal antibodies in transplantation. Unfortunately, initial promise in animal models gave way to disappointment in clinical trials following a number of thromboembolic complications. However, recent mechanistic studies have identified the mechanism of these adverse events, as well as detailed a myriad of interactions between CD40 and CD154 on a wide variety of immune cell types and the critical role of this pathway in generating both humoral and cell-mediated alloreactive responses. This has led to resurgence in interest and the potential resurrection of anti-CD154 and anti-CD40 antibodies as clinically viable therapeutic options.