Fig. 6: CAR T-cell studies in mice.

a NSG mice were injected intravenously with MM.1 S cells. After 10 days, 1 × 10⁶ T cells expressing the indicated CARs were injected intravenously. Mice were imaged every 3 days. Two experiments of five mice each were completed with similar results with cells from different donors. b, c RPMI8226 cells were injected intradermally into NSG mice. After palpable tumors were established, mice were injected intravenously with b 2 × 10⁶ or c 1 × 10⁶ T cells expressing the indicated CARs. Left side graphs show the mean tumor volume of five mice/group. The right side graphs show Kaplan–Meier plots of survival of the same mice. For the 2 × 10⁶ CAR T-cell dose, there was a statistically significant difference in survival between the T cells expressing the SP6-CD828Z negative-control CAR and 11D5-3-CD8BBZ, FHVH33-CD828Z, and FHVH33-CD8BBZ (P = 0.003 for all three comparisons). For the 1 × 10⁶ CAR T-cell dose, there was a statistically significant difference in survival between the T cells expressing the SP6-CD828Z negative-control CAR and 11D5-3-CD8BBZ, FHVH33-CD828Z, and FHVH33-CD8BBZ (P = 0.002 for all three comparisons). Two experiments of five mice/group each were completed with T cells from different donors for each experiment with 2 × 10⁶ CAR⁺ T cells/mouse. d CD3⁺CD4⁺CAR⁺ and e CD3⁺CD8⁺CAR⁺ splenocytes were quantitated by flow cytometry 10 days after infusion of FHVH33-CD828Z (28) or FHVH33-CD8BBZ (BB) T cells. The NSG mice had disseminated MM.1 S tumor cells established prior to intravenous CAR T-cell infusion. Comparison by Mann–Whitney test. P = 0.0011 for the CD4 comparison, and P = 0.0030 for the CD8 comparison. Bars represent medians; n = 8 mice per group.