Immunotherapy

1. TCR Identification and TCR      Immunotherapy Strategy

l  We have successfully developed an integrated technological platform that combines T cell epitope identification with the functional assessment of specific T cell responses. Utilizing HLA-A transgenic mouse models—including HLA-A02, -A24, and -A11—this platform enables T cell immune studies that encompass the genetic background of over 90% of the Chinese population. Additionally, we established a single-cell-based TCR screening technique and constructed a robust evaluation system to assess the functionality and tumor-suppressive efficacy of TCR-T cells (Frontiers in Immunology, 2021).

Figure 4. T cell immune research platform.

l  TCRs specifically targeting the KRAS-G12V mutation were successfully identified, and the structural basis underlying TCR recognition of KRAS mutations was further elucidated. Tumor-bearing mouse models have demonstrated that these TCR-T cells exhibit potent tumor-suppressive activity, laying a critical foundation for breakthroughs in KRAS mutation-targeted immunotherapy (Nature Communications, 2023). Currently, this project has been transferred for preclinical development and now under IIT clinical investigations in collaboration with hospitals.

l  Focusing on the predominant HLA subtypes in the Chinese population, the research team has identified TCRs specific for HLA-A11- and HLA-A24-restricted epitopes for KRAS mutant antigens, as well as MAGE-A4 and HPV-E6 antigens (Molecular Immunology, 2024). Notably, an exploratory clinical study targeting synovial sarcoma and other conditions using MAGE-A4 antigen-specific TCR-T cells tailored for the HLA-A11 genetic background was initiated on December 23, 2024.

Figure 5. Recognition of TCR to KRAS mutation and TCR immunotherapy