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嵌合抗原受体 T 细胞疗法:靶向肿瘤干细胞的前景。

CAR-T therapy: Prospects in targeting cancer stem cells.

机构信息

Basic Laboratory, Suining Central Hospital, Suining, China.

Department of Breast and Thyroid Surgery, Suining Central Hospital, Suining, China.

出版信息

J Cell Mol Med. 2021 Nov;25(21):9891-9904. doi: 10.1111/jcmm.16939. Epub 2021 Sep 28.

Abstract

Cancer stem cells (CSCs), a group of tumour cells with stem cell characteristics, have the ability of self-renewal, multi-lineage differentiation and tumour formation. Since CSCs are resistant to conventional radiotherapy and chemotherapy, their existence may be one of the root causes of cancer treatment failure and tumour progression. The elimination of CSCs may be effective for eventual tumour eradication. Because of the good therapeutic effects without major histocompatibility complex (MHC) restriction and the unique characteristics of CSCs, chimeric antigen receptor T-cell (CAR-T) therapy is expected to be an important method to eliminate CSCs. In this review, we have discussed the feasibility of CSCs-targeted CAR-T therapy for cancer treatment, summarized current research and clinical trials of targeting CSCs with CAR-T cells and forecasted the challenges and future direction from the perspectives of toxicity, persistence and potency, trafficking, infiltration, immunosuppressive tumour microenvironment, and tumour heterogeneity.

摘要

癌症干细胞(CSCs)是一群具有干细胞特征的肿瘤细胞,具有自我更新、多向分化和肿瘤形成的能力。由于 CSCs 对常规放化疗具有抗性,它们的存在可能是癌症治疗失败和肿瘤进展的根源之一。消除 CSCs 可能对最终消除肿瘤有效。由于嵌合抗原受体 T 细胞(CAR-T)治疗具有良好的治疗效果,不受主要组织相容性复合体(MHC)限制,以及 CSCs 的独特特性,预计它将成为消除 CSCs 的重要方法。在这篇综述中,我们讨论了针对 CSCs 的 CAR-T 治疗癌症的可行性,总结了目前用 CAR-T 细胞靶向 CSCs 的研究和临床试验,并从毒性、持久性和效力、归巢、浸润、免疫抑制肿瘤微环境和肿瘤异质性等方面预测了挑战和未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6707/8572776/e76b93dc05d4/JCMM-25-9891-g001.jpg

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