Figure 5. Affinity-tuned ErbB2 CART cells increase the therapeutic index and induce regression of advanced vascularized tumors in mice.
(a) In vivo discrimination of high ErbB2 (SK-OV3) and low ErbB2 (PC3) expressing tumors by affinity tuned CARs. T cells modified with different affinity ErbB2 CARs by lentiviral transduction were tested in dual-tumor engrafted NSG mice. Mice (n=5) were implanted with PC3-CBG tumor cells (1×106 cells/mouse, s.c.) on the right flank on day 0. On day 5 the same mice were given SK-OV3-CBG tumor cells (5×106 cells/mouse, s.c.) on the left flank. The mice were treated with T cells (i.v.) at day 23 after PC3 tumor inoculation. CART cells were given as a single injection of 1×107/mouse (10M), or 3×106/mouse (3M) as indicted. Mice treated with non-transduced T cells served as control. Animals were imaged at the indicated time post PC3 tumor inoculation. (b) SK-OV3 tumor size (left panel) or PC3 tumor sizes (right panel) in dual-tumor grafted NSG mice treated with the indicated ErbB2 CAR. Tumor sizes were measured, and the tumor volume was calculated and plotted. (c) Biostatistics analysis results for the tumor size. Data (not transformed) was analyzed for day < 56 (PC3) or day < 52 (SKOV3). Method was mixed models, with day, group, and day x group interaction as fixed effects, and mouse as random effect. For random effect, each mouse had a separate intercept and slope. (Method also known as random coefficients.) p-values presented are interaction p-values.