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靶向 TM4SF1 的 CAR-T 细胞构建及其在卵巢癌中的抗肿瘤能力

英文原题:Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer.

查看英文原题

Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer.

PubMed 2023/02/03(内容时间) Immunol Lett Q3 · IF 3.2(JCR 2025)

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中文摘要

卵巢癌(OC)是致死率最高的妇科恶性肿瘤,平均5年生存率为49.1%。临床实践中,减瘤术和化疗仍是晚期OC的常规治疗。然而,总体预后仍不佳,迫切需要肿瘤医师开发新疗法。作为免疫疗法的一个分支,嵌合抗原受体(CAR)T细胞疗法已成功治疗血液系统恶性肿瘤。TM4SF1是多种肿瘤中的潜在生物标志物,已证实在卵巢癌中高表达。本研究构建了第三代靶向TM4SF1的CAR-T 细胞药物治疗卵巢癌。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,并在体内抑制SKOV3来源肿瘤生长。这是首次报告靶向TM4SF1的CAR-T 疗法用于卵巢癌。结果提示TM4SF1可能是治愈OC的极有前景靶点,并显示TM4SF1靶向免疫疗法的潜力。

展开英文摘要原文

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 rd 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.

论文信息

作者
Shen Y、Liu G、Zhang Q、Tian X、Ouyang L、Zhang L
第一作者单位
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.China
通讯作者单位
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China. Electronic address: ouyanglm@ecust.edu.cn.China
文献类型
非美国政府资助研究
期刊
Immunology letters2023 Mar
原文标识
PubMed 36739093 · DOI 10.1016/j.imlet.2023.01.011