BCMA-SLAMF7- or BCMA-FAP-CART cells show a long-term durable response and improve overall survival in the MM-TME mouse model. (A-B) Four weeks after the injection of 1 × 10⁶ OPM-2 and 1 × 10⁶ BM-CAFs, mice were randomized into 4 groups: (1) UTD, (2) BCMA-CART cells, (3) BCMA-SLAMF7-CART cells, or (4) BCMA-FAP-CART cells. Tumor burden was assessed by using BLI (4 mice per group). (C) BLI curves of the MM-TME mouse models treated with UTD, single BCMA-CART-, dual-targeted BCMA-SLAMF7-, or BCMA-FAP-CART cells (mean and standard error of the mean; *P < .05, two-way analysis of variance at day 14). (D) Kaplan-Meier survival curves of the MM-TME mouse models treated with UTD, single BCMA-CART-, dual-targeted BCMA-SLAMF7-, or BCMA-FAP-CART cells (BCMA-CART- vs BCMA-SLAMF7-CART cells hazard ratio, 0.03020 [95% confidence interval, 0.001835-0.4969; *P = .01]; BCMA-CART- vs BCMA-FAP-CART cells hazard ratio, 0.03020 [95% confidence interval, 0.001835-0.4969; *P = .01]). (E-F) Mice were bled on day 10 after T-cell infusion. T-cell expansion (E) was analyzed with flow cytometry, and TGF-β levels were analyzed with singleplex (F). Absolute number of T cells per microliter was calculated with counting beads (mean and standard error of the mean; *P < .05, **P < .005, ****P < .0001, one-way analysis of variance). (G) Immunohistochemical analysis of BM samples from MM-TME mice treated with CART cells targeting BCMA, BCMA-SLAMF7, or BCMA-FAP (upper left, upper middle, lower left, and lower middle, magnification ×40; upper right and lower right, magnification ×20). n.s., not significant.