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

IF 5 2区 医学 Q2 Medicine Translational Oncology Pub Date : 2024-09-09 DOI:10.1016/j.tranon.2024.102111
Miaomiao Zhang , Haiting Wang , Meng Wang , Haoliang Zhang , Huizhong Li , Ping Ma , Junnian Zheng , Gang Wang , Shibao Li
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Abstract

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-γ 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.

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用于治疗前列腺癌的 EphA2 特异性嵌合抗原受体工程 T 细胞
促红细胞生成素肝细胞受体 A2(EphA2)在包括前列腺癌在内的多种实体瘤中高表达,因此是一种极具吸引力的免疫疗法靶点。在各种免疫疗法中,嵌合抗原受体T(CAR-T)细胞疗法在血液肿瘤和实体瘤中取得了可喜的进展。在此,我们检测了EphA2在前列腺癌细胞中的表达,并开发了以EphA2为靶点、CD28为辅助刺激受体的第二代CAR,以探索其在体外和体内对前列腺癌的抑瘤潜力。EphA2在PC3和DU145细胞表面高度表达。EphA2 CART细胞在体外和体内以抗原依赖的方式有效抑制了前列腺癌的生长。此外,肿瘤细胞还能在体外刺激 CAR-T 细胞的增殖和细胞因子 IFN-γ 的释放。这些发现揭示了EphA2是前列腺癌的潜在靶点,有望将EphA2特异性CAR-T细胞用于治疗前列腺癌。
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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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