Application of CAR-T cell therapy based on nano-delivery system in ovarian cancer

Ovarian cancer is one of the common malignant tumours in women. Approximately 70% of patients will still relapse within 2-3 years after conventional treatment. While tumor-associated glycoprotein-72(TAG-72) is more expressed in ovarian cancer compared with normal ovarian tissue and is associated with a worse prognosis, and there are ongoing clinical trials of TAG-72-directed CAR-T cells. Chimeric antigen receptor T cell (CAR-T cell) therapy is a new and promising immune approach in hematologic tumors while for solid tumors faces problems, such as difficulty in targeting infiltration, tumor antigen evasion, immunosuppressive environment, and potential toxic side effects. These problems will directly affect the efficacy of CAR-T cells, and the PD-1 pathway seems to be the master switch in all immunosuppressive signaling pathways, so we develop a model in which we propose to use Crispr-Cas9 technology to excise the PD-1 expressed by CAR-T cells in TAG-72-directed CAR-T, and at the same time, it will be encapsulated by nanomaterial IR780, which can be precisely located to the cancer nest through PTT (photothermal therapy), effectively supporting immune escape. Thereby, the reprogrammed CAR-T cells may effectively avoid cytokine storms. By developing this model, we hope to provide a new protocol for CAR-T therapy for ovarian cancer, which is expected to prolong overall survival.