Abstract
Triple-negative breast cancer (TNBC) is a very aggressive malignant type of tumor that currently lacks effective targeted therapies. In hematological malignancies, chimeric antigen receptor T (CAR-T) cells have shown very significant antitumor ability; however, in solid tumors, the efficacy is poor. In order to apply CAR-T cells in the treatment of TNBC, in this study, constitutively activated IL-7 receptor (C7R) that has been reported is used to enhance the antitumor function of constructed CAR-T cells by ourselves. Using in vitro coincubation experiments with target cells and in vivo antitumor experiments in mice, we found that the coexpressed C7R can significantly improve the activation, cell proliferation, and cytotoxicity of CAR-T cells. In addition, the in vivo experiments suggested that the enhanced CAR-T cells displayed significant antitumor activity in a TNBC subcutaneous xenograft model, in which in vivo, the survival time of CAR-T cells was prolonged. Together, these results indicated that CAR-T cells that coexpress C7R may be a novel therapeutic strategy for TNBC.
Highlights
Breast cancer is the most common malignant tumor in women; triple-negative breast cancer (TNBC) accounts for 15%–20% of the total incidence of breast cancer [1], which is more aggressive than other breast cancer subtypes [2]
Our findings showed that chimeric antigen receptor T (CAR-T) cells with constitutive expression of constitutively activated IL-7 receptor (C7R) had significant antitumor activity against TNBC, which overcame the limitations of traditional CAR-T cells in the treatment of solid tumors and provided a novel strategy for the treatment of TNBC
To avoid additional activation of the paired receptor in the extracellular domain of the IL-7 receptor, the natural extracellular domain of the receptor was substituted by the extracellular domain of CD34 to construct a recombinant receptor for CD34-IL7R∗, which was denoted as C7R (Figure 1(c))
Summary
Breast cancer is the most common malignant tumor in women; triple-negative breast cancer (TNBC) accounts for 15%–20% of the total incidence of breast cancer [1], which is more aggressive than other breast cancer subtypes [2]. When compared with CD19-CAR-T cells, the therapeutic effects of CAR-T cells on solid tumors are poor due to poor activity and the short survival time of CAR-T cells in solid tumors [7, 8]. To solve these problems, identifying novel techniques to enhance the antitumor ability of CAR-T cells in solid tumors is urgently warranted. In preclinical studies, it was demonstrated that genetically modified T cells resulted in IL-7 secretion or IL-7 receptor overexpression, thereby achieving enhanced antitumor effects [11].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
