Abstract
Lymph nodes (LNs) are essential tissues in generating and modulating effective immune responses. In this study, we investigated the intra-lymphatic delivery of immunotherapy cues encapsulated in degradable microparticles (MPs). We demonstrate that co-localization of antigens and adjuvants within the same lymph node generates robust antigen-specific T cell responses and significant anti-tumor protection, while spatial separation of cargos across different lymph nodes diminishes immune efficacy. While co-encapsulation of signals in the same particle within a lymph node ensures efficient delivery of both cargos, immune function is equally effectively when particles carrying a single cue are mixed and localized in the same node. This finding demonstrates a strategy for focused, potent responses in lymph nodes using degradable particles that offer attractive translational features, including the flexibility to load individual immunotherapeutic cargos into particles, followed by mixing prior to administration. This feature dramatically simplifies chemistry and manufacturing control (CMC) processes needed for development by avoiding manufacture of candidate immunotherapies that require simultaneous tuning of pharmacokinetic profiles.