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EphA2 特异性嵌合抗原受体工程化 T 细胞用于前列腺癌治疗

英文原题:EphA2 specific chimeric antigen receptor engineered T cells for the treatment of prostate cancer.

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EphA2 specific chimeric antigen receptor engineered T cells for the treatment of prostate cancer.

PubMed 2024/09/09(内容时间) Transl Oncol Q2 · IF 4.9(JCR 2025)

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中文摘要

促红细胞生成素产生肝细胞受体A2(EphA2)因其在包括前列腺癌在内的多种实体瘤中高表达,成为免疫治疗的一个有吸引力的靶点。在各种类型的免疫治疗中,CAR-T(CAR-T)细胞疗法在血液肿瘤和实体瘤中已取得令人瞩目的进展。在此,我们检测了EphA2在前列腺癌细胞中的表达,并开发了以CD28作为共刺激受体的第二代靶向EphA2的CAR,以探讨其在体外和体内对前列腺癌的肿瘤抑制潜力。EphA2在PC3和DU145细胞表面高表达。EphA2 CAR-T 细胞在体外和体内以抗原依赖的方式有效抑制前列腺癌生长。此外,肿瘤细胞可在体外刺激CAR-T 细胞增殖和细胞因子IFN-的释放。这些发现揭示了EphA2作为前列腺癌潜在靶点的前景,使EphA2特异性CAR-T 细胞有望用于前列腺癌的治疗。

展开英文摘要原文

Erythropoietin-producing hepatocyte receptor A2 (EphA2) is an attractive target for immunotherapy due to its high expression in a variety of solid tumors including prostate cancer. Among various types of immunotherapeutics, chimeric antigen receptor T (CAR-T) cell therapy has made promising progress in hematological and solid tumors.

Here, we detected the expression of EphA2 in prostate cancer cells and developed a second-generation CAR targeting EphA2 with CD28 as a co-stimulatory receptor to explore its tumor suppressive potential for prostate cancer in vitro and in vivo. EphA2 was highly expressed on the surface of PC3 and DU145 cells. EphA2 CART cells effectively inhibited prostate cancer growth in an antigen-dependent manner in vitro and in vivo.

In addition, tumor cells could stimulate the proliferation of CAR-T cells and the release of cytokine IFN- in vitro.

These findings shed light on EphA2 as a potential target for prostate cancer, promising EphA2 specific CAR-T cells for the treatment of prostate cancer.

论文信息

作者
Zhang M、Wang H、Wang M、Zhang H、Li H、Ma P、Zheng J、Wang G
第一作者单位
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, China.China
通讯作者单位
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: sdjnshlb@xzhmu.edu.cn.China
期刊
Translational oncology2024 Dec
原文标识
PubMed 39255722 · DOI 10.1016/j.tranon.2024.102111