CAR T cell immunotherapy of epithelial ovarian cancer: past, present and a view of the horizon

Abstract

Women diagnosed with ovarian cancer often face a poor prognosis, particularly owing to late diagnosis. The treatment of this highly lethal malignancy has remained largely unaltered over the last few decades and novel strategies to combat the disease are urgently needed. As it is considered an “immunologically cold” tumor, harnessing strategies that overcome immunosuppressive barriers that operate in this cancer may lead to improved therapeutic impact. One such approach entails the use of chimeric antigen receptor (CAR) T cell therapy. In brief, T cells are re-targeted to selected tumor-specific antigens in a human leukocyte antigen (HLA)-unrestricted manner, endowing the cells with potent signaling capacity. Impressive success has been achieved using CAR T cells to treat selected hematological malignancies. However, these cells encounter several additional hurdles when targeting solid tumors. Nevertheless, numerous studies have designed strategies to improve responses to CAR T therapy of solid tumors. Outlined in this review are CAR T cell-based approaches that have been evaluated in the treatment of ovarian cancer. We discuss both pre-clinical and available clinical data on the effects of these therapies against a range of ovarian cancer targets that include folate receptor a, mesothelin, MUC16, the ErbB family of receptors and ligands of the NKG2D receptor.