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

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology Pub Date : 2025-03-14 DOI:10.1016/j.imbio.2025.152888

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

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引用次数: 0

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.

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靶向B7-H3的实体肿瘤：新型CAR-T细胞疗法的发展和评估

卵巢癌和胃癌作为许多实体肿瘤的代表，由于治疗选择有限和晚期预后不佳，仍然是最具挑战性的恶性肿瘤之一。尽管免疫疗法已经彻底改变了癌症治疗，但它们在实体肿瘤中的疗效一直受到抗原异质性和免疫抑制肿瘤微环境等问题的阻碍。本研究提出了靶向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的选择性细胞毒性，不影响正常组织。在临床前动物模型中，这些细胞显著抑制肿瘤生长，表现出更高的靶向特异性和在肿瘤部位的优先积累。这些结果突出了b7 - h3靶向CAR-T细胞作为实体肿瘤免疫治疗的潜在突破，为未来的临床试验提供了基础，以完善其安全性和有效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunobiology 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

108

审稿时长

55 days

期刊介绍： Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.