Fig. 2: T cells expressing the CD19-specific full ChTCR recognize CD19low tumor cells and have superior antitumor effect in vivo.
a, Flow histograms of CD19 expression in Nalm-6 cell variants. b, IL-2 concentration in supernatants after coculture of T cells expressing each indicated receptor with Nalm-6 CD19high, CD19mid and CD19low cells at a 1:1 E/T ratio. Data are shown as the mean ± s.d. for three independent experiments. P values were calculated using a two-way ANOVA. c, IFNγ concentration in supernatants for each experimental group described in b. Data are shown as the mean ± s.d. for three independent experiments. P values were calculated using a two-way ANOVA. d, Left: representative histograms of CTV dye dilution in T cells expressing the indicated receptors after coculture with Nalm-6 CD19mid and Nalm-6 CD19low tumor cells. Right: percentage of divided cells (mean ± s.d.) for three independent experiments. P values were calculated using a two-way ANOVA. e, Left: western blot (WB) of LAT pTyr220, actin and LAT after coculture of CD8+ T cells expressing each indicated receptor with Nalm-6 CD19low tumor cells. Right: heat map of the mean band intensity of LAT pTyr220 normalized to the total LAT control (n = 3 independent experiments). f, Schematic of the Raji GFP-ffLuc+ NSG mouse model. g, Representative bioluminescence images of Raji-ffLuc tumor burden in NSG mice treated with 2 × 106 T cells expressing each indicated receptor (D, day). h, Tumor burden (mean ± s.d. radiance (photons per s per cm2 per steradian (sr))) of Raji GFP-ffLuc+ tumor-bearing NSG mice treated as in f (n = 3 mice per control group or 4 mice per treatment group; three independent experiments). i, Kaplan–Meier survival of Raji GFP-ffLuc+ tumor-bearing NSG mice treated as in f (n = 14 mice per treatment group). P values were calculated using a log-rank test. Ratios indicate mouse survival. j, Schematic of the Nalm-6 CD19low GFP-ffLuc+ NSG model. k, Representative bioluminescence images of Nalm-6 CD19low GFP-ffLuc+ tumor-bearing NSG mice treated with 2 × 106 T cells expressing the indicated receptors (n = 5 mice per group). l, Tumor burden (mean ± s.d. radiance (photons per s per cm2 per sr)) 18 days after treatment (n = 5 mice per group). P values were calculated using a nonparametric Kruskal–Wallis test. m, Kaplan–Meier survival of NSG mice treated as described in j (n = 5 mice per group). Mouse icons in f and j created with BioRender.com.
