Targeting cancer stem cells with CAR-based immunotherapy: biology, evidence, and future directions.

IF 6 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-07-28 DOI:10.1186/s12935-025-03846-3

Kaveh Hadiloo, Parsa Mostanadi, Ali Asadzadeh, Siavash Taremi, Abdolreza Esmaeilzadeh

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Abstract

Cancer stem cells (CSCs) are pivotal in tumor initiation, progression, and relapse, underscoring the need for targeted therapies to achieve lasting responses. This review delves into CSC biology, highlighting their tumor-initiating potential demonstrated through limiting dilution assays and their role in resistance to therapies. Although successful CAR therapies, such as anti-CD19 CAR T-cells, can induce complete responses without directly targeting CSCs, CAR strategies focusing on CSCs may offer promising avenues to prevent recurrence. We assess CAR therapies targeting CSC-specific antigens, including CD133 and GD2, in preclinical and clinical contexts, emphasizing their effectiveness against glioblastoma, breast cancer, and other malignancies. Nevertheless, challenges such as marker specificity and suppression by the tumor microenvironment (TME) persist. Future strategies, which may include dual-targeting and AI-driven marker discovery, aim to improve CSC elimination and advance personalized cancer immunotherapy.

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靶向肿瘤干细胞的CAR-based免疫疗法：生物学、证据和未来方向。

肿瘤干细胞（CSCs）在肿瘤的发生、进展和复发中起着关键作用，因此需要靶向治疗来实现持久的疗效。这篇综述深入研究了CSC生物学，强调了它们通过限制稀释试验证明的肿瘤启动潜力及其在治疗耐药性中的作用。尽管成功的CAR疗法，如抗cd19 CAR - t细胞，可以在不直接靶向CSCs的情况下诱导完全缓解，但专注于CSCs的CAR策略可能为预防复发提供了有希望的途径。我们在临床前和临床环境中评估了靶向csc特异性抗原（包括CD133和GD2）的CAR疗法，强调了它们对胶质母细胞瘤、乳腺癌和其他恶性肿瘤的有效性。然而，诸如标记特异性和肿瘤微环境（TME）抑制等挑战仍然存在。未来的策略可能包括双靶向和人工智能驱动的标记物发现，旨在改善CSC消除和推进个性化癌症免疫治疗。

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

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.