The importance of the CD40 pathway in T1D immunosuppression strategies is well-documented. Here the authors present the development of a novel monoclonal antibody, called 2C10, to block the CD40 pathway as a T1D immune therapy. Monkeys were treated with 2C10 or a placebo before being injected with a protein antigen to cause an immune reaction. Treatment with 2C10 successfully inhibited T cell-dependent antibody responses. Subsequently, the monkeys underwent islet transplantation and received standard immunosuppression therapies with or without 2C10. Islet graft survival was significantly prolonged in animals receiving 2C10 compared to those who did not. The survival advantage conferred by treatment with 2C10 provides further evidence for the importance of blockade of the CD40 pathway in preventing immune responses following islet transplantation. 2C10 is a particularly attractive candidate for translation to clinical studies given its favorable clinical profile.
A Novel Monoclonal Antibody to CD40 Prolongs Islet Allograft Survival. Am J Transplant. 2012 Aug; 12(8):2079-87.
Investigators and Institutions:
This work was led by Drs. Kirk and Larsen at Emory University.
Ramifications for Individuals with Type 1 Diabetes:
Islet transplantation has been shown to have great efficacy in T1D individuals, but its availability is limited. This research helps develop a novel immunosuppressive reagent for use in islet transplantation.
This work was supported in part by JDRF.