Abstract
Ovarian cancer (OC) is the most lethal gynecological malignancy and is responsible for most gynecological cancer deaths. Apart from conventional surgery, chemotherapy, and radiotherapy, chimeric antigen receptor-modified T (CAR-T) cells as a representative of adoptive cellular immunotherapy have received considerable attention in the research field of cancer treatment. CARs combine antigen specificity and T-cell-activating properties in a single fusion molecule. Several preclinical experiments and clinical trials have confirmed that adoptive cell immunotherapy using typical CAR-engineered T cells for OC is a promising treatment approach with striking clinical efficacy; moreover, the emerging CAR-Ts targeting various antigens also exert great potential. However, such therapies have side effects and toxicities, such as cytokine-associated and “on-target, off-tumor” toxicities. In this review, we systematically detail and highlight the present knowledge of CAR-Ts including the constructions, vectors, clinical applications, development challenges, and solutions of CAR-T-cell therapy for OC. We hope to provide new insight into OC treatment for the future.
Highlights
Ovarian cancer (OC) is the second most common gynecological malignancy in the United States, with 21,290 new cases in 2015, and the most frequent cause of gynecological cancer-related mortality, with 14,180 estimated deaths in the same year [1]
We present an overview of the biological understanding, clinical applications, and challenges of chimeric antigen receptor-modified T (CAR-T)-cell therapy in OC
This paper describes frequently used viral approaches—gamma retroviral, lentiviral, adenovirus, and adeno-associated viral vectors—as well as nonviral approaches such as liposomal-mediated gene transfer, messenger RNA–mediated gene transduction and Sleeping Beauty transposon/transposase system. (Table 1)
Summary
Ovarian cancer (OC) is the second most common gynecological malignancy in the United States, with 21,290 new cases in 2015, and the most frequent cause of gynecological cancer-related mortality, with 14,180 estimated deaths in the same year [1]. Human T cells modified to express CARs specific for FRα have been reported to exhibit effective antitumor activity in vitro and in animal models; their effects on clinic patients appear to be weak due to their inability to persist and home in on tumor sites [11, 106]. Despite its potential and promising clinical results, CAR-T-cell immunotherapy involves several toxicities because of the presentation of tumor-associated antigens by healthy tissues and the inability to control T-cell activity. Despite intensive medical intervention, she died 5 days after treatment The death of this patient was speculated to be a result of the infusion of highly active anti-ERBB2-directed CAR-T cells, which recognized ERBB2 expressed by normal lung epithelial cells and released inflammatory cytokines (TNF-α and IFN-γ) that caused pulmonary toxicity and multiorgan failure [131]. They discovered that increased surface expression of HIFCARs along with improved cytolytic properties of T cells can be obtained under hypoxic conditions
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