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:B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer.
B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer.
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B7-H3 在包括前列腺癌在内的多种实体瘤中高表达、在正常组织中表达受限,因此是有吸引力的免疫治疗靶点。在多种肿瘤免疫疗法中,CAR-T(CAR-T)细胞治疗血液系统肿瘤已取得显著成功,但其治疗实体瘤的效力仍有限。本研究检测前列腺癌组织和细胞中的 B7-H3 表达,并开发一种特异性靶向 B7-H3、以 CD28 为共刺激受体的第二代 CAR,以体内外评估其前列腺癌杀伤潜力。PC3、DU145 和 LNCaP 细胞表面及前列腺癌组织均检测到高水平 B7-H3 表达。B7-H3 CAR-T 细胞以抗原依赖性方式在体内外有效控制前列腺癌生长。此外,体外肿瘤细胞可诱导 CAR-T 细胞增殖,并释放高水平 IFN-γ 和 TNF-α。结果表明,B7-H3 是前列腺癌治疗的潜在靶点,支持临床开发靶向 B7-H3 的前列腺癌 CAR-T 细胞疗法。
B7-H3 is an attractive target for immunotherapy because of its high expression across multiple solid tumors, including prostate cancer, and restricted expression in normal tissues. Among various types of tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematological tumors.
However, the potency of CAR-T cell therapy in solid tumors is still limited.
Here, we examined the expression of B7-H3 in prostate cancer tissues and cells and developed a second-generation CAR that specifically targets B7-H3 and CD28 as costimulatory receptor to explore its tumoricidal potential against prostate cancer in vitro and in vivo. The high expression of B7-H3 was detected on both the surface of PC3, DU145 and LNCaP cells and prostate cancer tissues. B7-H3 CAR-T cells efficiently controlled the growth of prostate cancer in an antigen-dependent manner in vitro and in vivo.
Moreover, tumor cells could induce the proliferation of CAR-T cells and the release of high levels of cytokines of IFN- and TNF- in vitro. Results demonstrated that B7-H3 is a potential target for prostate cancer therapy that supports the clinical development of B7-H3 specific CAR-T cells for prostate cancer.
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