Fig. 4: BCMA/CS1 OR-gate CAR-T cells prevent antigen escape in vivo.

a Evaluation of single-input and bispecific CAR-T cells in vivo. Mice were engrafted with a mixture of 1.5 × 10⁶ MM.1 S cells containing a 1:1:1 ratio of BCMA⁺/CS1⁻, BCMA⁻/CS1⁺, and BCMA⁺/CS1⁺ cells. Tumor-bearing animals were treated with 1.5 × 10⁶ EGFRt- or CAR-expressing T cells on day 5 (5 days after tumor injection) and day 13. Six mice were included in each initial treatment group but only five mice in the huLuc63-c11D5.3 group were redosed due to limited T-cell availability. Tumor progression was monitored by bioluminescence imaging. b Survival of mice shown in a. Statistical difference (depicted) between survival of huLuc63-c11D5.3-treatment group compared with other treatment groups was determined using log-rank analysis, applying a Chi-square distribution with one degree of freedom; n.s. not statistically significant (p > 0.05); *p < 0.05; **p < 0.01. P-values for the different treatment groups are as follows: Untreated, p = 0.024; EGFRt, p = 0.024; Luc90, p = 0.011; huLuc63, p = 0.015; c11D5.3, p = 0.008; huc11D5.3-Luc90, p = 0.114. c BCMA/CS1 antigen expression on tumors harvested from mice treated with CS1 single-input Luc90 Short, huLuc63 Long, or BCMA single-input c11D5.3 Long CAR-T cells. Values shown are the means of n = 4 technical replicates for cells stained prior to injection. Thirteen to 18 tumor samples were collected from different locations in the mice (six mice per test group) at the time of sacrifice, with error bars indicating +1 standard deviation (SD), and each sample corresponding to 100 or more events as detected by flow cytometry. d Antigen expression pattern on tumor cells recovered at the time of animal sacrifice. Each data point d corresponds to an individual tumor sample recovered that included more than 100 tumor cells as detected by flow cytometry; each mouse generally contained multiple tumors at the time of sacrifice. Source data are provided as a Source Data File.