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靶向实体瘤中的B7-H3:新型嵌合抗原受体T细胞疗法的开发与评估。

Targeting B7-H3 in solid tumors: Development and evaluation of novel CAR-T Cell therapy.

作者信息

Li Ning, Zhang Chunhua, Li Xiaoyu, Liu Shufen, Xu Youhua, Yang Xifei

机构信息

Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa 999078, Macao.

Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa 999078, Macao; The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.

出版信息

Immunobiology. 2025 May;230(3):152888. doi: 10.1016/j.imbio.2025.152888. Epub 2025 Mar 14.

Abstract

Ovarian and gastric cancers, representative of many solid tumors, remain among the most challenging malignancies to treat due to limited therapeutic options and poor outcomes at advanced stages. Although immunotherapies have revolutionized cancer treatment, their efficacy in solid tumors has been hindered by issues such as antigen heterogeneity and the immunosuppressive tumor microenvironment. This study presents the development and evaluation of third-generation chimeric antigen receptor T (CAR-T) cells targeting B7-H3, an immune checkpoint molecule widely overexpressed in solid tumors. The B7-H3 CAR-T cells exhibited robust and selective cytotoxicity against B7-H3-positive tumor cells, sparing normal tissues. In preclinical animal models, these cells significantly inhibited tumor growth, demonstrating higher targeting specificity and preferential accumulation in tumor sites. These results highlight B7-H3-targeted CAR-T cells as a potential breakthrough in immunotherapy for solid tumors, offering a foundation for future clinical trials to refine their safety and efficacy.

摘要

卵巢癌和胃癌是许多实体瘤的代表,由于治疗选择有限且晚期预后不佳,仍然是最难治疗的恶性肿瘤之一。尽管免疫疗法彻底改变了癌症治疗方式,但其在实体瘤中的疗效受到抗原异质性和免疫抑制性肿瘤微环境等问题的阻碍。本研究展示了靶向B7-H3的第三代嵌合抗原受体T(CAR-T)细胞的开发和评估,B7-H3是一种在实体瘤中广泛过度表达的免疫检查点分子。B7-H3 CAR-T细胞对B7-H3阳性肿瘤细胞表现出强大且选择性的细胞毒性,对正常组织无损伤。在临床前动物模型中,这些细胞显著抑制肿瘤生长,显示出更高的靶向特异性和在肿瘤部位的优先聚集。这些结果突出了靶向B7-H3的CAR-T细胞作为实体瘤免疫治疗潜在突破的地位,为未来临床试验优化其安全性和疗效奠定了基础。

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