Local control of T cell fate in lymph nodes safely and durably reverses myelin-driven autoimmunity
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (22)
Senta M. Kapnick
Robert E. Fischell Institute for Biomedical Devices, University of Maryland
Emily A. Gosselin
Fischell Department of Bioengineering, University of Maryland
Shannon J. Tsai
Fischell Department of Bioengineering, University of Maryland
Robert S. Oakes
Robert E. Fischell Institute for Biomedical Devices, University of Maryland
Zahra A. Habibabady
Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital
Marian A. Ackun-Farmmer
Robert E. Fischell Institute for Biomedical Devices, University of Maryland
Sean T. Carey
Robert E. Fischell Institute for Biomedical Devices, University of Maryland
Shrey A. Shah
Robert E. Fischell Institute for Biomedical Devices, University of Maryland
Ruochen Shen
Robert E. Fischell Institute for Biomedical Devices, University of Maryland
Eugene Froimchuk
Fischell Department of Bioengineering, University of Maryland
Haleigh B. Eppler
Fischell Department of Bioengineering, University of Maryland
Christopher J. Bridgeman
Robert E. Fischell Institute for Biomedical Devices, University of Maryland
Alexis A. Yanes
Fischell Department of Bioengineering, University of Maryland
Ryan A. McIlvaine
Robert E. Fischell Institute for Biomedical Devices, University of Maryland
Maeesha Noshin
Fischell Department of Bioengineering, University of Maryland
Lisa H. Tostanoski
Fischell Department of Bioengineering, University of Maryland
Sheneil K. Black
Fischell Department of Bioengineering, University of Maryland
Xiangbin Zeng
Fischell Department of Bioengineering, University of Maryland
Agnes Azimzadeh
Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital
Richard N. Pierson
Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital
Jonathan S. Bromberg
Department of Surgery, University of Maryland School of Medicine
Christopher M. Jewell
Robert E. Fischell Institute for Biomedical Devices, University of Maryland