构建靶向 TM4SF1 的 CAR-T 细胞及其在卵巢癌中的抗肿瘤能力。
Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer.
机构信息
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China; Shanghai Yihao Biological Technology Co., Ltd., Shanghai, 200231, China.
出版信息
Immunol Lett. 2023 Mar;255:1-9. doi: 10.1016/j.imlet.2023.01.011. Epub 2023 Feb 3.
Ovarian cancer (OC) is the most lethal gynecological malignancy with a 5-year survival rate of 49.1% on average. In clinical practice, cytoreduction and chemotherapy remain the conventional treatment for advanced OC. However, the overall prognosis remains poor, which urges oncologists to develop new treatments. Chimeric antigen receptor (CAR)-T therapy as a branch of immunotherapy had gained a success in treating hematological malignancies. TM4SF1, a potential biomarker in many tumors, was validated highly expressed in ovarian cancer. Here we constructed a 3 generation CAR-T agent targeting TM4SF1 to treat ovarian cancer. CAR-T cells showed a specific cytotoxicity against TM4SF1 positive tumor cell lines in vitro and repressed SKOV3-derived tumor growth in vivo. This is the first time reporting a CAR-T therapy targeting TM4SF1 in ovarian cancer. Our results suggested that TM4SF1 could be a very promising target in curing OC and showed the possibility of TM4SF1-based immunotherapy.
卵巢癌（OC）是最致命的妇科恶性肿瘤，平均 5 年生存率为 49.1%。在临床实践中，肿瘤细胞减灭术和化疗仍然是治疗晚期 OC 的常规方法。然而，整体预后仍然较差，这促使肿瘤学家开发新的治疗方法。嵌合抗原受体（CAR）-T 疗法作为免疫疗法的一个分支，在治疗血液系统恶性肿瘤方面取得了成功。TM4SF1 是许多肿瘤中的一个潜在生物标志物，已被验证在卵巢癌中高表达。在这里，我们构建了一种针对 TM4SF1 的第三代 CAR-T 药物来治疗卵巢癌。CAR-T 细胞在体外对 TM4SF1 阳性肿瘤细胞系表现出特异性细胞毒性，并抑制了 SKOV3 衍生的肿瘤生长。这是首次报道靶向 TM4SF1 的 CAR-T 疗法治疗卵巢癌。我们的结果表明，TM4SF1 可能是治疗 OC 的一个很有前途的靶点，并显示了基于 TM4SF1 的免疫疗法的可能性。
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