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实体瘤的细胞疗法:挑战与进展

英文原题:Cell-Based Therapies for Solid Tumors: Challenges and Advances.

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Cell-Based Therapies for Solid Tumors: Challenges and Advances.

PubMed 2025/06/09(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

实体瘤因其对传统治疗的耐药性以及肿瘤微环境的复杂性,构成了重大的治疗挑战。基于细胞的免疫疗法提供了一种有前景的方法,通过免疫系统调节实现精准、个性化的治疗。本综述探讨了针对实体瘤的几种新兴细胞疗法,包括TIL(肿瘤浸润淋巴细胞)、T 细胞受体工程化 T 细胞、CAR-T 细胞、CAR NK 细胞和巨噬细胞。TIL(肿瘤浸润淋巴细胞)及其改造版本、T 细胞受体工程化 T 细胞和 CAR-T 细胞可提供个性化的免疫应答,尽管其有效性可能受到肿瘤抗原变异和肿瘤环境抑制性等因素的限制。经嵌合受体工程化的NK 细胞提供了更安全、非主要组织相容性复合体限制性的靶向作用,而改造后的巨噬细胞则利用其进入肿瘤并重塑免疫格局的天然能力。CAR 修饰的巨噬细胞和偶联药物的巨噬细胞也被视为实体瘤的治疗手段。本综述还探讨了自体与异体细胞来源的意义。自体疗法确保了免疫相容性,但受限于可扩展性和生产制造方面的制约。异体方法具有“即用型”潜力,但需要基因编辑以避免免疫排斥。整合合成生物学、基因编辑和组合策略对于提高疗效并拓展细胞免疫疗法在实体瘤中的临床应用至关重要。

展开英文摘要原文

Solid tumors pose significant therapeutic challenges due to their resistance to conventional treatments and the complexity of the tumor microenvironment. Cell-based immunotherapies offer a promising approach, enabling precise, personalized treatment through immune system modulation. This review explores several emerging cellular therapies for solid tumors, including tumor-infiltrating lymphocytes, T cell receptor-engineered T cells, CAR T cells, CAR natural killer cells, and macrophages. Tumor-infiltrating lymphocytes and their modified versions, T cell receptor-engineered T cells and CAR T cells, provide personalized immune responses, although their effectiveness can be limited by factors like variation in tumor antigens and the suppressive nature of the tumor environment.

Natural killer cells engineered with chimeric receptors offer safer, non-major histocompatibility complex-restricted targeting, while modified macrophages exploit their natural ability to enter tumors and reshape the immune landscape. CAR-modified macrophages and macrophages conjugated with drugs are also considered as therapy for solid tumors. The review also examines the implications of autologous versus allogeneic cell sources.

Autologous therapies ensure immunologic compatibility but are limited by scalability and manufacturing constraints. Allogeneic approaches offer "off-the-shelf" potential but require gene editing to avoid immune rejection. Integrating synthetic biology, gene editing, and combinatorial strategies will be essential to enhance efficacy and expand the clinical utility of cellular immunotherapies for solid tumors.

论文信息

作者
Smolarska A、Kokoszka Z、Naliwajko M、Strupczewska J、Tondera J、Wiater M、Orzechowska R
第一作者单位
Center of Cellular Immunotherapies, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.Poland
通讯作者单位
Faculty of Biology and Biotechnology, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.Poland
文献类型
综述
期刊
International journal of molecular sciences2025 Jun 9
原文标识
PubMed 40564987 · DOI 10.3390/ijms26125524