Commentary: Ovarian Cancer: Path to Effective Treatments

Despite advancements in cancer therapeutics such as checkpoint inhibitors and some targeted therapies, we have not achieved success in effectively treating ovarian cancer, since these therapeutics only benefit a subset of patients, and also provide short-term protection. The use of chemotherapy and radiation therapy can cause depletion and/or lack of immune cells' function. Chimeric antigen receptor T (CAR-T) cell therapy is found to be effective against several blood-based cancers, but limited success was seen against solid tumors. Targeting fewer antigens and significant side effects of therapy decreases the efficacy of CAR-T cells as immunotherapeutic in solid tumors, even though there is a great drive and significant effort to establish these therapies around the world. Bispecific and tri-specific antibodies have recently been advocated as effective cancer therapeutics. However, at present, these also suffer the fate of CAR-Ts since the loss of antigen on tumor cells will render these therapeutics ineffective. At present, we should design therapeutics that may have synergistic effects on killing/treating tumors. The only way we can establish that will be by learning the mechanisms of actions of immune therapeutics. Thus, advancement in the knowledge and effective strategies are required to develop cancer immuno-therapeutics. We have dedicated our efforts to understand the immunobiology of natural killer (NK) cells. One of our most important discoveries was demonstration of targeting of cancer stem-like cells (CSCs)/poorly differentiated tumors exhibiting lower major histocompability complex class I expression by the NK cells. In addition, we showed that supercharged NK (sNK) cells had great ability to target both CSCs/poorly differentiated and well differentiated ovarian tumors, whereas activated primary NK cells only targeted CSCs/poorly differentiated tumors. Therefore, the use of sNK cells in immunotherapy should result in effective elimination of heterogeneous populations of ovarian tumors.