Abstract IA06: Enhancing combination immunotherapy and adoptive cell therapy of cancer via lymph node-targeted vaccines

Abstract

Abstract Lymph node targeting is achieved clinically is sentinel lymph node mapping in cancer patients, where small-molecule dyes are efficiently delivered to lymph nodes by binding to serum albumin. To mimic this process in vaccine delivery, we synthesized amphiphile-vaccines (lipid-polymer conjugates of peptides, proteins, or molecular adjuvants) designed to non-covalently bind vaccine antigens and adjuvants to endogenous albumin. These amphiphile conjugates both protect peptide antigens from premature degradation and greatly increase their delivery to lymph nodes. Such “albumin-hitchhiking” amphiphiles elicited as much as 30-fold amplified cellular immune responses and antitumor immunity against multiple antigens, and further enable mucosal delivery of therapeutic vaccines through albumin-mediated transport across epithelial barriers via the neonatal Fc receptor. When combined with complementary immunotherapy agents, these lymph node-targeted vaccines are capable of eradicating large established tumors in several mouse models, providing a blueprint for curative immunotherapies. We have further demonstrated that amph-vaccines can be used to deliver ligands for chimeric antigen receptor (CAR) T cells to lymph nodes, creating efficient booster vaccines for CAR T cells. Citation Format: Darrell J. Irvine. Enhancing combination immunotherapy and adoptive cell therapy of cancer via lymph node-targeted vaccines [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA06.