Abstract 5581: A genetically modified tumor-infiltrating lymphocytes product (GT202) exhibits enhanced persistence and anti-tumor efficacy against solid tumor in vivo

Abstract

Abstract Adoptive cell therapy by tumor-infiltrating lymphocytes (TILs) has demonstrated significant clinical benefits for patients with solid tumors. However, the toxicities related to high-dose IL-2 that is required to support TIL survival and the exhaustion status of the final TIL product after rapid expansion in culture largely limits the clinical application and long-term efficacy of TIL therapy. Grit Biotechnology designed a genetically engineered TIL product (GT202) to express a membrane-bound cytokine that is critical for T cell activation and effector function, leading to enhanced cytotoxicity as well as persistence in vitro and in vivo. Multiple designs of the transmembrane domain of GT202 were compared and the best design was selected based on stable and efficient expression of GT202 on the membrane of TILs. GT202 demonstrated significantly increased cytotoxicity and cytokine production when cocultured with tumor cells in vitro than conventional TILs and better tumor control ability during a serial killing assay. In the meanwhile, GT202 TILs showed enhanced long-term survival and better preservation of TCR clonality without IL-2 in vitro, as well as persisted longer in multiple tissues without IL-2 over conventional TILs + IL-2 in NGS mice. Notably, GT202 TILs achieved better anti-tumor efficacy with low IL-2 in NSG mice inoculated with HLA-matched tumor cells than conventional TILs, corelated with their better infiltration and proliferation in spleen and tumor. In summary, GT202 demonstrated enhanced anti-tumor efficacy and persistence as well as decreased IL-2 dependency in vitro and in vivo. Currently, an investigator-initiated trial of GT202 is ongoing in China. Citation Format: Jingwei Sun, Jiahui Jin, Yongchao Tan, Lingyun Chen, Quanwei Wang, Yarong Liu. A genetically modified tumor-infiltrating lymphocytes product (GT202) exhibits enhanced persistence and anti-tumor efficacy against solid tumor in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5581.