Building immune tolerance with a novel recombinant Adv5-TIGIT vector 2598

Abstract Description tolerance is the “holy grail” in the fields of transplantation medicine and the treatment of autoimmune diseases. We previously reported that TIGIT+ B cells can efficiently control inflammatory responses while promoting regulatory T cell response via the ligation of CD155 expressed on both T cells and dendritic cells (DCs). Recent studies have also demonstrated that lack of TIGIT expression in B cells can lead to inflammation in the central nervous system in both humans and mice. These findings prompted us to explore whether TIGIT+ B cell therapy model could be developed for the treatment of inflammatory diseases. In this study, we report that TIGIT+ B cells can be generated with replication-incompetent recombinant Adv5 vectors designed to target CD21 on B cells. Those TIGIT+ B cells generated with our novel Adv5 vectors can efficiently control inflammatory T cell responses in vitro by directly acting on T cells and by regulating inflammatory function of DCs. The preclinical efficacy of TIGIT+ B cell therapy model and its underlying mechanisms of action are also investigated using an experimental autoimmune encephalomyelitis model. Data from this study support the clinical development of this novel TIGIT+ B cell therapy model for the treatment of inflammatory diseases. Funding Sources Mayo Clinic Cancer Center Topic Categories Therapeutic Approaches to Autoimmunity (THER)