A catalogue of Ovarian Cancer targets for CAR therapy.
2020
Ovarian Cancer (OC) is currently difficult to cure, mainly due to its late detection and the advanced state of the disease at the time of diagnosis. Therefore, conventional treatments such as debulking surgery and combination chemotherapy are rarely able to control progression of the tumour, and relapses are frequent. Alternative therapies are currently being evaluated, including immunotherapy and advanced T-cell based therapy. In the present review, we will focus on a description of those Chimeric Antigen Receptors (CARs) that have been validated in the lab, or are being tested in the clinic. Numerous target antigens have been defined due to the identification of OC biomarkers, and many are being used as CAR targets. We provide an exhaustive list of these constructs and their current status. Despite being innovative and efficient, the OC-specific CARs face a barrier to their clinical efficacy: the tumour microenvironment (TME). Indeed, effector cells expressing CARs have been shown to be severely inhibited, rendering the CAR T cells useless once at the tumour site. Herein we give a thorough description of the highly immunosuppressive OC-TME, and present recent studies and innovations that have enabled CAR T cells to counteract this negative environment and to destroy tumours.
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