Fig. 1
PARP inhibitors promote tumor regression for RCC models under low-dose CD70 CAR-T cell treatment. a Schemas of CD70-CARs incorporating different spacers [CD8α Signal peptide, CD8α Hinge, (G4S)3 Linker, and CD8α™] and costimulatory domains (4-1BB). b Lysis of spheres of 786-0 target cell cultures in the presence of CD70 CAR-T cells, or Mock CAR-T cells (control) at a 1:1, 2:1, 4:1, 8:1 effector/target ratio. (Scale bar: 250 μm) c A real-time cytotoxicity assay (xCElligence RTCA SP) was used to evaluate the lysis of the indicated tumor cells when treated with mock CAR-T (E−) cells or CAR-T (E+) cells at the indicated E/T ratios over a 50-h period. Representative of three independent experiments. d ELISA results showed the IL-2, TNF-α and IFN-γ secretion levels by CD70 CAR-T (E+), mock CAR-T (E−) cells encountering 786-0 cell. e Subcutaneous renal cell carcinoma tumor (786-0) development was monitored by in vivo bioluminescence imaging (5 × 106 CAR-T cells/mice). Images taken at dpi. 0, 8, 10 are shown (exposure time of 40 s). f Data showing the tumor volume (mm3) change trend of B-NDG mice xenograft 786-0 tumor regression/growth in 4 different treat groups. g Kaplan–Meier survival curve was performed 140 days after 786-0 cells injection. Mice treated with CD70 CAR-T cells had a significantly longer survival probability in comparison with mice treated with PBS, T or mock CAR-T cells. h ELISA results showed the IL-2, TNF-α and IFN-γ secretion levels in mice blood treated by PBS, T, mock CAR-T, CD70 CAR-T cells. i Treatment scheme used in the 786-0 xenograft model treated with OLA and CAR-T cells. j B-NDG mice were treated with OLA and 2.5 × 106 CAR-T cells/mice. Subcutaneous renal cell carcinoma tumor (786-0) development was monitored by in vivo bioluminescence imaging. Images taken at dpi. 0, 3, 6, 9, 20 are shown (exposure time of 40 s). k Data showing the tumor volume (mm3) change trend of B-NDG mice in 5 different treat groups. l Mice body weights monitored during treatment. m Kaplan–Meier survival curve was performed 150 days after 786-0 cells injection. Mice treated with CD70 CAR-T cells had a significantly longer survival probability in comparison with mice treated with T + Vehicle (DMSO), olaparib (OLA), T + OLA, CAR-T + Vehicle, CAR-T + OLA. n–p ELISA results showed the IL-2, TNF-α and IFN-γ secretion levels in mice blood treated by T + Vehicle, OLA, T + OLA, CAR-T + Vehiele, CAR-T + OLA. q CD70 CAR-T cells in peripheral blood were detected using flow cytometry on day15 after CAR-T inoculation. All error bars represent SD. In all plots, ns, not significant; *, p < 0.05; **, p < 0.01; ***, p < 0.001