Co-localization of immune cargos in lymph nodes enhances T cell activation and anti-tumor immunity 9359

Description Cancer vaccination is an immunotherapy approach that stimulates the immune system to recognize and attack tumor-specific antigens. Like traditional vaccines, these therapies contain adjuvants to elicit and amplify immune response. Yet, as tumor are elusive and suppressive, achieving effective responses – including co-delivery of adjuvant and relevant tumor antigens is challenging. Lymph nodes (LNs) are essential tissues in generating and modulating immune response. Engineering these the local LN microenvironments during cancer vaccination could enable a potent new treatment strategy. We hypothesized that direct co-localization of antigen and adjuvant in LNs define therapeutic outcome of cancer vaccination. We tested this hypothesis by designing microparticle (MP) depots loaded with model antigens (ovalbumin, OVA) and a molecular adjuvant – a toll-like receptor (TLR) agonist (polyIC) that activates immune cells. We then used intra-lymph node (i.LN.) injection of degradable, diffusion-limited MPs that are too large to drain from LNs after injection to directly control cancer vaccine deposition. We demonstrated that co-localization of OVA and PolyIC within the same lymph node, regardless of tumor location, generates robust antigen-specific T cell responses and significant anti-tumor protection during B16-OVA melanoma. These results suggest direct lymph node priming with these depots can enable potent tumor therapy that does not require knowledge of tumor location. Funding Sources This work was supported in part by NIH # R01AI169686 and MPowering the State of Maryland. Topic Categories Vaccines and Immunotherapy (VAC)