Defined distribution and features of lymph node therapies enable recruitment and manipulation of antigen-specific T cell response.

Abstract

Antigen-specific therapies to treat autoimmune diseases would benefit from improved understanding of the conditions needed to efficiently and selectively modulate inflammatory response. By leveraging the unique features of a spatially restricted platform to deliver polymer depots to lymph nodes (LNs), we establish design and delivery parameters required to locally regulate antigen-specific response. We show depots containing peptides and regulatory or stimulatory cues introduced directly to LNs recruit and engage antigen-specific T cells in treated LN microenvironments. This selectivity is maintained even during the administration of formulations containing multiple antigens, and the nature of this response can be switched between tolerizing or activating responses by defining cues in depots. Notably, in a myelin-driven model of autoimmunity, local depots promote re-polarization of inflammatory antigen-specific T cells into regulatory T cells. Efficacy against autoimmune disease is dose dependent but with low sensitivity to formulation parameters such as cargo-loading density and the ratio of antigen and modulatory cues in depots. This work defines cardinal features and delivery considerations for next-generation antigen-specific immunotherapies targeting autoimmune disease.