Senta M. Kapnick, Emily A. Gosselin, Shannon J. Tsai, Robert S. Oakes, Zahra Habibabady, Marian A. Ackun‐Farmmer, Sean T. Carey, Shrey Shah, Ruochen Shen, Eugene Froimchuk, Haleigh B. Eppler, Christopher J. Bridgeman, Alexis A. Yanes, Ryan A. McIlvaine, Maeesha Noshin, Lisa H. Tostanoski, Sheneil K. Black, Xiangbin Zeng, Agnes M. Azimzadeh, Richard N. Pierson, Jonathan S. Bromberg, Christopher M. Jewell
Development of tolerogenic, antigen-specific immunotherapies could overcome limitations of existing treatments for inflammatory autoimmune diseases by achieving potent, durable remission without impacting healthy immune surveillance. Here, we deliver diffusion-limited polymer depots to lymph nodes to locally guide T cell fates for the treatment of multiple sclerosis (MS), an autoimmune disease that occurs when the immune system mistakenly attacks myelin. In preclinical MS models, depots loaded with myelin self-antigen and tolerizing cues mediate localized retention of activated CD4 T cells, promote myelin-specific regulatory T cells, and reshape inflammation in the central nervous system (CNS) to eliminate lesions. Selective disease reversal is achieved with a single treatment that induces long-lasting remission without hindering healthy responses to vaccine challenge with foreign antigen. Furthermore, depots offer favorable chemistry and manufacturing control features and are well tolerated in non-human primates. This work supports a clinically feasible concept for inducing safe, effective, antigen-specific tolerance without systemic or repeated dosing.