In vivo strategy to induce tolerance to therapeutic proteins and autoantigens

Induced immunity to therapeutic proteins and autoimmunity to native proteins both represent major sources of disease pathology and barriers to effective disease-modifying treatments. It is well appreciated that induction of immune tolerance to these exogenous and auto-antigens holds promise to prevent therapy-limiting immune responses and rescue autoimmune disease. However, potent strategies to affect such antigen-specific tolerance have remained elusive. In this project, we will test a new and exciting possibility for driving immune tolerance to both exogenous proteins and endogenous autoantigens. Leveraging our group’s extensive expertise in gene therapy, we will test the hypothesis that our approach, focused on modulating T cell development in vivo, can promote tolerance to both disease-causing and therapeutic proteins.  If successful, the work pursued under this pilot award will provide novel, proof-of-concept evidence in support of a unique approach for subverting detrimental immune responses to combat autoimmune disease and promote successful cell and gene therapies.