Abstract 6438: Next-generation pan-cancer immunotherapy with patient-derived APC

Abstract Harnessing phagocytic antigen presenting cells (APC) and tumor neoantigen-specific T cells represent the ultimate power of immunotherapy against cancer. The promises of phagocytic APCs lie in their abilities of not only initiating phagocytosis towards cancer cells (to “eat off” tumor) but also, through immunogenic antigen presentation, activating neoantigen-specific Tcells that systemically and durably eliminate cancer cells, as well as the establishment of a long-lasting cellular and hormonal immunity that prevents tumor recurrence. However, the efforts of developing APCs -based therapy have been hindered by the current lack of technology that robustly produce APCs from cancer patients, as none of the traditional methods for differentiating DC or macrophage APCs are effective for cancer patients. Through a proprietary process, we have created a unique reagent combo that enables robust differentiation of cancer patients’ peripheral monocytes (cMo) to be potent APC, termed κAPC. κAPC display a unique gene expression profile, separating from classical DC or macrophage, and profound proinflammatory phenotype with enhanced phagocytic capability and elevated immunogenic antigen presentation machinery. In both in vitro and in vivo settings, κAPC demonstrate direct uptake of tumor antigens and presentation to T cells, the latter leading to activation and large expansion of multi-targeting, polyclonal tumor-specific CD4 and CD8 T populations - termed NeoT- from circulating and tumor-infiltrating lymphocytes. Theexpanded CD8 NeoT are highly tumoricidal and once adoptively transferred in vivo, potently eliminated late-stage metastatic solid tumors, whereas CD4 NeoT contribute to immune memory and repolarize a proinflammatory TME favorable for tumor elimination. Key words: κAPC, NeoT, NeoT adoptive cell therapy, κAPC-based cancer vaccine, combination therapies Citation Format: Zhen Bian, Lei Shi, Yuan Liu, harry Stylli. Next-generation pan-cancer immunotherapy with patient-derived APC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6438.