Abstract LB340: Spur cell-delivered peptide antigen generates T cell immunity to eradicate mouse KRASG12D spontaneous lung cancer

Abstract

Abstract Red blood cells (RBCs) have been widely used in delivering various drugs including cancer antigens. However, due to their inherent biocompatibility and low immunogenicity, RBC-based tumor antigen delivery often fails to initiate anti-tumor immunity and results in lower clinical efficacy of cancer vaccines. Here we report that tumor antigen-encapsulated RBCs can be rapidly transformed to spur cells which have much higher immunogenicity. Compared to normal RBCs, spur cells display a defused surface CD47 pattern with a lower affinity to SIRPα, and thus can be rapidly engulfed by activated macrophages and dendritic cells. The tumor antigen-loaded spur cells elicit high antigen responses both in vitro and in vivo. In combination with the SHP-1 inhibitor, spur cell-delivered KRASG12D antigenic peptides markedly suppress tumor growth in KRASG12D spontaneous mouse lung cancer model. In addition, a specific T cell population targeting the KRASG12D mutated peptide antigen is detected in cancer-survival mice. Our study thus has developed spur cell-delivered cancer neoantigen as an effective cancer vaccine. Citation Format: Shuang Qu, Jiafan Wang, Meng Jia, Hongwei Liang, Yuan Liu, Ke Zen. Spur cell-delivered peptide antigen generates T cell immunity to eradicate mouse KRASG12D spontaneous lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB340.