Abstract 2471: State-of-the-art Specific T cell Activating Modulator on ePENDY platform (STAM.eP) activates specific CD8+ T cell by stimulating TCR signal

Abstract

Abstract After decades of research, therapeutic cancer vaccine approach now sheds light on developing efficient cancer therapy treating patients who have resistance to other cancer immunotherapy. However, cancer vaccine approach using conventional modalities such as protein, peptide, and mRNA is considered a powerful cancer treatment only when the patients have healthy immune systems. In addition, dendritic cell (DC) cancer vaccine can be a great alternative therapy, but manufacture of DC vaccines in vitro is a labor-intensive, time- and money-consuming procedure. Here, we developed Specific T cell Activating Modulator (STAM) on our engineered IgM backbone, ePENDY (engineered PENtamer boDY), with high avidity based on multivalent binding sites to overcome the disadvantages of other therapeutic cancer vaccines. STAM on ePENDY (STAM.eP) consists of ten peptide-loaded-HLAs linked to ePENDY to simulate priming signal of CD8+ T cell by TCR cluster and a costimulatory signal molecule is linked to J chain of ePENDY to prevent CD8+ T cell from becoming anergic status. With these features, STAM.eP mimics cognately licensed DC that can present tumor peptide-loaded MHC class I molecule to CD8+ T cell and promote its priming. Thus, one of the greatest advantages of STAM.eP is to be a potential treatment for immunosuppressive cancer patients with DCs that do not respond appropriately. Another advantage is that any tumor specific antigen (TSA), including from intracellular proteins, can be applied to STAM.eP concept to activate specific CD8+ T cells for targeting cancer cells. In this study, we used Human Papillomavirus (HPV) E7-derived peptide which is an oncoprotein associated with cervical and head/neck cancers. We observed that HPV E7-derived peptide loaded STAM.eP, named IMB-401, increases antigen-specific CD8+ T cell population and shows cytotoxicity activity against cancer cells expressing HPV E7 protein in vitro test model. In vivo test model, it was also observed that population of specific CD8+ T cells and memory T cells were increased in the blood and spleens of transgenic mice treated with IMB-401. Furthermore, we confirmed that IMB-401 shows anti-tumor efficacy due to an increase of antigen-specific CD8+ T cell in vivo humanized mouse model. These results suggest that IMB-401 can be a new therapeutic cancer vaccine technology that replaces DC function and is expected to have robust anti-tumor activity in combination with immune checkpoint inhibitors. Citation Format: Kyung-gi Hyun, Sungmuk Kang, Yongjun Kang, Jihye Koo, Suho Park, Sunghyun Byun, Sunghyun Yoon, Jaebeom Lee, Hong Jai Lee, Hong Kyu Lee, Eunyoung Cho, Chungmin Lee, Kyung-Chul Choi, Gyongsik Ha. State-of-the-art Specific T cell Activating Modulator on ePENDY platform (STAM.eP) activates specific CD8+ T cell by stimulating TCR signal [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2471.