Figure 4.
Olaparib Enhances the Anti-tumor Activity of CAR-T Cells in Mice Bearing 4T1EGFRvIII Tumor Cells
(A) In vivo experimental design. 4T1EGFRvIII tumor cells (5 × 105) were in situ inoculated into BABL/c mice and allowed to establish for 14 days. Mice were assigned to four experimental groups and PBS or olaparib (50 mg/kg) was administered via intraperitoneal injection for 10 days. CAR-T cells were injected i.v. on day 21. (B–E) Tumor growth (B), body weight (C), tumor inhibition rate (D), and tumor weight (E) of each treatment group (n = 6). (F) CAR copy number in genomic DNA of residual tumors 10 days after therapy were measured by qRT-PCR (TaqMan probe). (G and H) The representative flow cytometry plots showing the (G) frequencies and (H) quantitations of tumor-infiltrating CD45+ immune cells and MDSCs of each treatment group. (I) The mRNA expression of iNOS and Arg-1 in 4T1EGFRvIII tumor tissue of mice. (J and K) The sections of formalin-fixed, paraffin-embedded tumor tissue from mice of each group were immunostained with anti-CD4, anti-CD8, or anti-CD31 Ab and H&E staining. The images were obtained under original magnification 200×. Scale bars, 100 μm. All data are presented as the mean ± SEM of triplicate experiments. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.