Fig. 5

Cytotoxicity of anti-MM UCAR-T cells against MM targeting cells in NCG xenograft models. (A) Schematic of the tumor models in which 2 × 10⁶ tumor cells were injected (i.v.). Mice received 5 × 10⁶ UCAR-T cells at day 0 and monitor tumor burden, body weight and survival. (B-C) RPMI-8226-mCherry.ffLuc and MM.1S-mCherry.ffLuc cells were injected i.v. into NCG mice, and treated beginning on day 0 with PBS, Nb5-UCART against CD123 and anti-MM UCAR-T cells (n = 5). MM cells were effectively limited in mice treated with monospecific and bispecific UCAR-T cells compared to Nb5-UCART cells and PBS control. (D-F) The levels of TNF-α, IFN-γ and IL-2 in mice treated with anti-MM UCAR-T cells was significantly higher than treated with Nb5-UCART cells against CD123 (n = 5). (G) The proportion of UCAR-T cells in the peripheral blood (PB) of mice showed no significant difference on day 24 after UCAR-T cells treatment (n = 5). (H) The proportion of mCherry cells in the PB of mice on day 24 after monospecific UCAR-T cells treatment was higher than BCMA/CD47-directed h32-UCART cells (n = 5). (I-J) Kaplan-Meier analysis showed the mice treated with BCMA/CD47-directed h32-UCART cells had significantly longer survival compared to treated with monospecific UCAR-T cells (hu388-UCART and hu404-UCART). A log-rank Mantel-Cox test was used to test for statistical significance. Data represent mean ± SD, statistical significance was determined by a one-way ANOVA with Tukey’s post-test. *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001; ns, no significance