Fig. 1: Stromal-targeted FAP-CAR T cells inhibit PDAC tumor growth more effectively than Meso-CAR T cells. | Nature Communications

Fig. 1: Stromal-targeted FAP-CAR T cells inhibit PDAC tumor growth more effectively than Meso-CAR T cells.

From: Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors

Fig. 1

a Depiction of control MigR, Meso-CAR and FAP-CAR recombinant MigR constructs. b–d Comparable transduction efficiency, CAR expression and function of FAP- and Meso-CAR T cells in vitro. b Flow cytometric analysis of EGFP expression (Y-axis) and reactivity with CAR binding APC-conjugated anti-F(ab’)2 fragment antibodies (X-axis). c Cytotoxic activity and d IFN-γ release when T cells were cultured with target cells expressing their specific targets, Meso+ 4662 tumor cells and murine FAP transfected 3T3 cells, relative to negative control Meso-KO 4662 cells and FAP-negative parental 3T3 cells, respectively (n = 3 independent samples/group). Data points are mean±SD and groups were compared using two-way ANOVA with Tukey’s multiple comparisons test. ****p < 0.0001. e–l Impact of FAP-CAR T vs. Meso-CAR T on growth of established 4662 tumors subcutaneously transplanted into syngeneic mice and (j–l) established spontaneous pancreatic tumors in KPC mice. e Experimental timeline for treatment of 4662 syngeneic PDAC tumor bearing C57BL/6 mice. Average (f) and individual (g) growth curves, tumor weight at endpoint (h) and modified Kaplan-Meier curves (i) for each treatment cohort in the syngeneic transplant model. j Schematic of KPC autochthonous tumor model experimental design. Average tumor growth curves measured by ultrasound (k) and modified Kaplan-Meier plots (l) for KPC mice with indicated treatments. Data indicate mean±SD (n = 5 per group) and were determined by one-way ANOVA with Tukey’s multiple comparisons test (f, h, and k) or log-rank test (i and l). j The pancreas and ultrasound are created with BioRender.com. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. h PBS vs. Meso-CAR, p = 0.032; PBS vs. FAP-CAR, p = 0.002; MigR vs. FAP-CAR, p = 0.010. i. PBS vs. Meso-CAR, p = 0.049; MigR vs. FAP-CAR, p = 0.004; Meso-CAR vs. FAP-CAR, p = 0.020. k. MigR vs. Meso-CAR, p = 0.029. The p values for remaining comparisons are all <0.001 or <0.0001. Source data are provided as a Source Data file.

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