Breast Internal Medicine Department, The 3rd Affiliated Teaching Hospital of XinJiang Medical University (Affiliated Cancer Hospital), Urumqi 830011, China.
Biomed Res Int. 2020 Jan 2;2020:4795171. doi: 10.1155/2020/4795171. eCollection 2020.
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 coincubation experiments with target cells and 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 experiments suggested that the enhanced CAR-T cells displayed significant antitumor activity in a TNBC subcutaneous xenograft model, in which , 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.
三阴性乳腺癌(TNBC)是一种非常侵袭性的恶性肿瘤,目前缺乏有效的靶向治疗方法。在血液恶性肿瘤中,嵌合抗原受体 T(CAR-T)细胞显示出非常显著的抗肿瘤能力;然而,在实体肿瘤中,疗效不佳。为了将 CAR-T 细胞应用于 TNBC 的治疗,在这项研究中,我们使用了已报道的组成型激活的白细胞介素 7 受体(C7R)来增强我们构建的 CAR-T 细胞的抗肿瘤功能。通过与靶细胞的共孵育实验和小鼠体内的抗肿瘤实验,我们发现共表达的 C7R 可以显著改善 CAR-T 细胞的激活、细胞增殖和细胞毒性。此外,实验表明,增强的 CAR-T 细胞在 TNBC 皮下异种移植模型中表现出显著的抗肿瘤活性,其中,CAR-T 细胞的存活时间延长。总之,这些结果表明共表达 C7R 的 CAR-T 细胞可能是 TNBC 的一种新的治疗策略。