CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer.
Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer.
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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。
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.
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