Effective antitumor activity of 5T4-specific CAR-T cells against ovarian cancer cells in vitro and xenotransplanted tumors in vivo

Ovarian cancer is considered to be the most lethal gynecologic malignancy, and despite the development of conventional therapies and new therapeutic approaches, the patient's survival time remains short because of tumor recurrence and metastasis. Therefore, effective methods to control tumor progression are urgently needed. The oncofetal tumor‐associated antigen 5T4 (trophoblast glycoprotein, TPBG) represents an appealing target for adoptive T‐cell immunotherapy as it is highly expressed on the surface of various tumor cells, has very limited expression in normal tissues, and spreads widely in malignant tumors throughout their development. In this study, we generated second‐generation human chimeric antigen receptor (CAR) T cells with redirected specificity to 5T4 (5T4 CAR‐T) and demonstrated that these CAR‐T cells can elicit lytic cytotoxicity in targeted tumor cells, in addition to the secretion of cytotoxic cytokines, including IFN‐γ, IL‐2, and GM‐CSF. Furthermore, adoptive transfer of 5T4 CAR‐T cells significantly delayed tumor formation in xenografts of peritoneal and subcutaneous animal models. These results demonstrate the potential efficacy and feasibility of 5T4 CAR‐T cell immunotherapy and provide a theoretical basis for the clinical study of future immunotherapies targeting 5T4 for ovarian cancer.
We generated a second‐generation CAR‐T cell targeting 5T4 with the costimulatory molecule of 4‐1BB. 5T4 CAR‐T cells had specific cytotoxicity against ovarian cancer cells and secreted cytotoxic cytokines, including IFN‐γ, IL‐2 and GM‐CSF in vitro. 5T4 CAR‐T cells could eradicate peritoneal and subcutaneous tumor models in vivo completely in a short time without recurrence.