Advancing CAR-based cell therapies for solid tumours: challenges, therapeutic strategies, and perspectives

IF 33.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2025-07-07 DOI:10.1186/s12943-025-02386-8

Sarkar Sardar Azeez, Raya Kh. Yashooa, Shukur Wasman Smail, Abbas Salihi, Azhin Saber Ali, Sami Mamand, Christer Janson

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Abstract

Chimeric antigen receptor-cell therapies have demonstrated remarkable success in haematological malignancies but face significant hurdles in solid tumours. The hostile tumour microenvironment, antigen heterogeneity, limited tumour infiltration, and CAR-cell exhaustion contribute to reduced efficacy. Additionally, toxicity, off-target effects, and manufacturing challenges limit widespread clinical adoption. Overcoming these barriers requires a multifaceted approach that enhances CAR-cell persistence, trafficking, and tumour-specific targeting. Recent advancements in alternative cellular therapies, such as CAR-natural killer cells, CAR-macrophages, gamma delta CAR-T cells, and CAR-natural killer T cells, provide promising avenues for improving efficacy. These strategies leverage distinct immune cell properties to enhance tumour recognition and persistence. Furthermore, combination therapies, including chemotherapy, radiotherapy, antibodies, small molecule inhibitors, cancer vaccines, oncolytic viruses, and multi-CAR cell combination therapy, offer synergistic potential by modulating the TME and improving CAR-cell functionality. This review explores the challenges of CAR-based cellular therapies in solid tumours and highlights emerging strategies to overcome therapeutic limitations. By integrating novel cellular platforms and combination approaches, we seek to provide insights into optimising CAR-cell therapies for durable responses in solid malignancies.

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推进基于car的实体肿瘤细胞疗法：挑战、治疗策略和观点

嵌合抗原受体-细胞疗法在血液系统恶性肿瘤中取得了显著的成功，但在实体肿瘤中面临重大障碍。不利的肿瘤微环境、抗原异质性、有限的肿瘤浸润和car细胞衰竭导致疗效降低。此外，毒性、脱靶效应和制造方面的挑战限制了广泛的临床应用。克服这些障碍需要多方面的方法来增强car细胞的持久性、运输和肿瘤特异性靶向。car -自然杀伤细胞、car -巨噬细胞、γ δ CAR-T细胞和car -自然杀伤T细胞等替代细胞疗法的最新进展为提高疗效提供了有希望的途径。这些策略利用独特的免疫细胞特性来增强肿瘤的识别和持久性。此外，联合疗法，包括化疗、放疗、抗体、小分子抑制剂、癌症疫苗、溶瘤病毒和多car细胞联合疗法，通过调节TME和改善car细胞功能提供协同潜力。这篇综述探讨了基于car的细胞疗法在实体肿瘤中的挑战，并强调了克服治疗局限性的新策略。通过整合新的细胞平台和联合方法，我们寻求为优化car细胞疗法提供见解，以实现实体恶性肿瘤的持久反应。

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

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.