Fig. 2: On-Target off-tumor toxicity of CLDN18.2 CAR-T cells is independent of co-stimulatory domain and CAR backbone, and correlates with CAR-T cell expansion.
From: On-target off-tumor toxicity of claudin18.2-directed CAR-T cells in preclinical models
A Experimental schematic (created in BioRender. Birocchi, F. (2025) https://BioRender.com/foaa417): In vivo testing of hu8e5-CD28z CAR-T cells in 5 different healthy donors (B-E). NSG mice were injected subcutaneously with 2 × 10⁶ GSU tumor cells. After 10 days, mice were treated intravenously with 3 × 10⁶ hu8e5-CD28z CAR-T cells or UTDs cells (donor 1) (n = 5 mice per group). B Tumor volume (mean ± s.d., 2-way ANOVA). C Body weight change compared to pre-treatment (mean ± s.d., 2-way ANOVA). D CAR-T cell transduction efficiency (flow cytometry). E Survival plot. F Absolute count of CAR-T cells in the peripheral blood at 7, 14, and 21 days post CAR-T cell injection. G–L in vivo experiment comparing VH/VL orientation (VH-VL vs. VL-VH) and transmembrane domains (CD28 vs. CD8) in hu8e5-CD28z CAR-T cells. G Schematic of vector maps used. H Experimental schematic (same as A, created in BioRender. Birocchi, F. (2025) https://BioRender.com/foaa417) (n = 5 mice per group). I Flow cytometry plot showing CAR-T cell transduction efficiency. J Tumor volume (mean ± s.d., 2-way ANOVA). K Body weight change (mean ± s.d., 2-way ANOVA). L Survival plot. M–R In vivo comparison of hu8e5 CAR-T cells with 4-1BB vs. CD28 co-stimulatory domains. M Schematic of vector maps used. N Experimental schematic (same as A, created in BioRender. Birocchi, F. (2025) https://BioRender.com/foaa417) (n = 2 healthy donors, n = 5 mice per group/donor). O Flow cytometry plot showing CAR-T cell transduction efficiency. P Body weight change (mean ± s.d., 2-way ANOVA). Q Tumor volume (mean ± s.d., 2-way ANOVA). R Survival plot.
