Fig. 3: Inducible IL-12 expression increases the activity of affinity-tuned Y6V CAR-T cells against GC.

a Lentiviral vectors encoding Y6V-iIL12 CAR and iIL-12 control construct. b–i NSG mice were inoculated with 1 × 10⁶ SNU-638 cells subcutaneously. 1 × 10⁷ non-transduced T (NT), UBS54, Y6V, Y6V-iIL12 or iIL-12 CAR-T cells were administered intravenously 7 days post-xenograft. b Representative bioluminescence images from one independent experiment (n = 5 mice/group). c Average whole-body BLI kinetics. d Average tumor volume measurements over time. Data represent mean ± SD. P-values were determined by Two-way ANOVA with Tukey’s multiple comparisons test. e Tumor growth curves for individual mice. f Percentage of mice with tumors < 300 mm³. P-value was determined by log-rank (Mantel–Cox) test. g Average body weight changes relative to baseline. Data represent mean ± SD. In c–g, no T cell treatment (No T), n = 10 mice examined over 3 independent experiments; Y6V, n = 10 mice examined over two independent experiments (2 donors); NT and Y6V-iIL-12, n = 13 mice examined over 3 independent experiments (3 donors); UBS54 and iIL-12, n = 5 mice examined over one independent experiment (1 donor). h PET-CT images showing CAR-T cell expansion and localization in tumor at 1-week after T cell treatment. Subcutaneous tumors are indicated by white arrow heads. n = 1 mouse/group. i Cytokine levels in mouse plasma measured at indicated timepoints post T cell injection. Data represent mean ± SD of 3 mice analyzed in one independent experiment. Statistical annotations reflect differences between Y6V-iIL-12 and Y6V determined by unpaired, two-tailed Student’s t-test.