Figure 4.

Performance of T cells transgenic for neoantigen-specific TCRs in vivo. (A) Growth kinetics of U-698-M tumors expressing neoantigens (area in mm²) in NSG mice. Mean values and SDs are depicted for each group of mice to monitor rejection dynamics (n=6). Animals were intravenously injected with a total of 2×10⁷ T cells on day 0+1. Tumor growth was significantly impaired in all mice receiving neoantigen-specific TCRs in comparison to 2.5D6 at day 10 (adjusted p value of 0.0001, calculated with two-way analysis of variance (time and treatment) and multiple comparison Dunnett’s test). (B) Kaplan-Meier survival curve of tumor-bearing mice injected with different TCR-transduced T cells. Survival of animals receiving neoantigen-specific TCRs was significantly prolonged to 2.5D6 (p<0.0001, Mantel-Cox test) (C), percentage of TCRmu⁺ T cells among all infiltrating CD3⁺CD8⁺ T cells in spleen, bone marrow and blood. Organs of animals receiving 2.5D6-transgenic T cells were processed at the respective day of removal. One control mouse receiving 2.5D6-transgenic T cells did not exhibit a clear population of infiltrating T cells and was therefore excluded from this analysis. All other animals with transferred neoantigen-specific TCR constructs were analyzed at day 20 exhibiting complete tumor rejection. TCR, T-cell receptor.