Steven Kim Wins AJT Award for Most Outstanding Article in Translational Science
General surgery resident Steven Kim, MD, who is engaged in transplant immunology research in the lab of transplant surgeon-scientist Andrew Adams, MD, PhD, received the American Journal of Transplantation's award for Best Translational Science Article of 2017 at the 2018 American Transplant Congress.
The article, "Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection," was co-authored with Dr. Kim by senior author Dr. Adams, other members of Dr. Adams' lab, and various faculty of the Emory Transplant Center, including Thomas Pearson, MD, DPhil, Chris Larsen, MD, DPhil, and Mandy Ford, PhD.
While the most effective costimulation blockade in experimental models of heart, kidney, and islet allografts has been the use of reagents to block the CD40/CD154 costimulatory pathway, thereby preventing long-term immune rejection, clinical translation of this method has been largely unsuccessful due to thromboembolic complications — the formation of a clot or clots that can break loose and plug other vessels.
In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, Dr. Kim and his team evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004) in a nonhuman primate kidney transplant model.
In addition to effectively blocking CD40-CD154 interactions, the team found that the anti-CD154 dAb did not generate the crystallizable fragment (Fc) binding activity that influences the platelet activation that precedes thromboembolism. They then combined the anti-CD154 dAb with conventional immunosuppression and reported that prevention of allograft rejection was strengthened even further.
Dr. Kim and his team concluded that the use of a novel anti-CD154 dAb that lacks Fc binding activity was safe, showed no evidence of thromboembolism, and was as potent as previous anti-CD154 agents at prolonging renal allograft survival in a nonhuman primate preclinical model, and showed potential for clinical application.