Through intra-lymph node (LN) injection, Andorko et al. localized OVA antigen and/or poly(I:C) adjuvant loaded in PLGA microparticles to distinct LNs, where they were taken up by DCs and macrophages. At an equivalent vaccine dose, systemic OVA-specific CD8+ T cell responses were strongest when a half-dose was delivered each to two LNs (“two”), compared to a full dose to one LN (“one”) or split antigen and adjuvant to separate LNs (“split”). OVA alone induced local LN OVA-specific T cells, but these did not circulate. Both one- and two-LN delivery protected from OVA+ tumor challenge; split only worked when adjuvant was delivered to the tumor-draining LN.
Contributed by Alex Najibi
ABSTRACT: Recently approved cancer immunotherapies - including CAR-T cells and cancer vaccination, - show great promise. However, these technologies are hindered by the complexity and cost of isolating and engineering patient cells ex vivo. Lymph nodes (LNs) are key tissues that integrate immune signals to coordinate adaptive immunity. Directly controlling the signals and local environment in LNs could enable potent and safe immunotherapies without cell isolation, engineering, and reinfusion. Here we employ intra-LN (i.LN.) injection of immune signal-loaded biomaterial depots to directly control cancer vaccine deposition, revealing how the combination and geographic distribution of signals in and between LNs impact anti-tumor response. We show in healthy and diseased mice that relative proximity of antigen and adjuvant in LNs - and to tumors - defines unique local and systemic characteristics of innate and adaptive response. These factors ultimately control survival in mouse models of lymphoma and melanoma. Of note, with appropriate geographic signal distributions, a single i.LN. vaccine treatment confers near-complete survival to tumor challenge and re-challenge 100 days later, without additional treatments. These data inform design criteria for immunotherapies that leverage biomaterials for loco-regional LN therapy to generate responses that are systemic and specific, without systemically exposing patients to potent or immunotoxic drugs.