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F77 抗原是前列腺癌过继性 T 细胞治疗的有潜力靶点

英文原题:F77 antigen is a promising target for adoptive T cell therapy of prostate cancer.

查看英文原题

F77 antigen is a promising target for adoptive T cell therapy of prostate cancer.

PubMed 2023/09/12(内容时间) Biochem Biophys Res Commun Q3 · IF 2.5(JCR 2025)

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中文摘要

利用嵌合抗原受体(CAR)T细胞进行过继免疫治疗,在血液系统恶性肿瘤中已取得显著成功,也为前列腺癌等实体瘤治疗铺平了道路,但适宜靶抗原匮乏仍限制着进展。新型糖类抗原F77表达于雄激素依赖性和非依赖性前列腺癌细胞表面,可能成为免疫治疗靶点。本研究针对恶性前列腺癌细胞上的糖类抗原构建并评估第二代CAR。研究采用F77特异性小鼠单克隆抗体的单链可变片段(scFv),构建含CD28或CD137(4-1BB)共刺激信号的第二代CAR。表达F77特异性CAR的慢病毒转导T细胞可产生细胞因子,并以依赖F77表达的方式杀伤肿瘤细胞。在采用PC3细胞的人源异种移植模型中,F77特异性CAR-T 细胞可清除前列腺肿瘤。这些发现验证了F77作为前列腺癌及其他表达该异常糖类结构的恶性肿瘤免疫治疗靶点的潜力。

展开英文摘要原文

Adoptive immunotherapy using chimeric antigen receptor (CAR) T cells has made significant success in treating hematological malignancies, paving the way for solid tumors like prostate cancer.

However, progress is impeded by a paucity of suitable target antigens. A novel carbohydrate antigen, F77, is expressed on both androgen-dependent and androgen-independent prostate cancer cells, making it a potential immunotherapy target.

This study entails the generation and evaluation of a second-generation CAR against a carbohydrate antigen on malignant prostate cancer cells. Using a single chain fragment variable (scFv) from an F77-specific mouse monoclonal antibody, we created second-generation CARs with CD28 and CD137 (4-1BB) costimulatory signals. F77 expressing lentiviral CAR T cells produce cytokines and kill tumor cells in a F77 expression-dependent manner. These F77-specific CAR T cells eradicate prostate tumors in a human xenograft model employing PC3 cells.

These findings validate F77 as a promising immunotherapeutic target for prostate cancer and other malignancies with this aberrant carbohydrate structure.

论文信息

作者
Grover P、Nunez-Cruz S、Leferovich J、Wentz T、Bagchi A、Milone MC、Greene MI
第一作者单位
Department of Pathology and Lab Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.United States
通讯作者单位
Department of Pathology and Lab Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: greenemarkirwin@gmail.com.United States
文献类型
非美国政府资助研究 · 美国 NIH 资助研究
期刊
Biochemical and biophysical research communications2023 Nov 5
原文标识
PubMed 37717341 · DOI 10.1016/j.bbrc.2023.09.018