OBJECTIVES: This study aimed to investigate the synergistic potential of TROP-2-targeted CAR-T cells combined with the vascular disrupting agent PLG-g-mPEG/CA4/BLZ945 (CBP). We hypothesized that CBP would disrupt the tumor neovascular, thereby enhancing infiltration of the CAR-T cells. METHODS: Analyzed TROP-2 expression in breast cancer using bioinformatics, qRT-PCR, and sequencing. Constructed and evaluated TROP-2 CAR-T cells in vitro. Finally, we prepared an animal model of breast cancer, and verified the anti-tumor therapeutic effect, safety evaluation and biologic mechanisms of TROP-2 CAR-T combined with CBP in vivo. RESULTS: Bioinformatics analysis and in vitro experiments showed that TROP-2 was widely expressed in breast cancer cells. The successfully constructed TROP-2 CAR-T cells exhibited high cytotoxicity in vitro. The experimental results in mice showed that the combination therapy of CBP and TROP-2 CAR-T significantly enhanced the anti-tumor effect, and no significant decrease in survival rate or major organ damage was observed. Mechanism studies have shown that the anti-tumor effect of the combination therapy group may be related to immune cell infiltration, CAR-T cell infiltration, and upregulation of immune related factors. CONCLUSION: Our findings demonstrated the potential of TROP-2 as a viable target for CAR-T therapy in breast cancer. The combination of TROP-2 CAR-T cells with CBP not only enhances the therapeutic efficacy but also maintains a favorable safety profile, offering a promising new strategy for the treatment of breast cancer.
Chen et al. (Fri,) studied this question.