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嵌合抗原受体(CAR)靶向免疫细胞在乳腺癌治疗中的潜力:最新进展。

Potential of chimeric antigen receptor (CAR)-redirected immune cells in breast cancer therapies: Recent advances.

机构信息

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Division of Nephrology & Hypertension, Department of Internal Medicine, Faculty of Medicine, Universitas Lambung Mangkurat / Ulin Hospital, Banjarmasin, Indonesia.

出版信息

J Cell Mol Med. 2022 Aug;26(15):4137-4156. doi: 10.1111/jcmm.17465. Epub 2022 Jun 28.

Abstract

Despite substantial developments in conventional treatments such as surgery, chemotherapy, radiotherapy, endocrine therapy, and molecular-targeted therapy, breast cancer remains the leading cause of cancer mortality in women. Currently, chimeric antigen receptor (CAR)-redirected immune cell therapy has emerged as an innovative immunotherapeutic approach to ameliorate survival rates of breast cancer patients by eliciting cytotoxic activity against cognate tumour-associated antigens expressing tumour cells. As a crucial component of adaptive immunity, T cells and NK cells, as the central innate immune cells, are two types of pivotal candidates for CAR engineering in treating solid malignancies. However, the biological distinctions between NK cells- and T cells lead to differences in cancer immunotherapy outcomes. Likewise, optimal breast cancer removal via CAR-redirected immune cells requires detecting safe target antigens, improving CAR structure for ideal immune cell functions, promoting CAR-redirected immune cells filtration to the tumour microenvironment (TME), and increasing the ability of these engineered cells to persist and retain within the immunosuppressive TME. This review provides a concise overview of breast cancer pathogenesis and its hostile TME. We focus on the CAR-T and CAR-NK cells and discuss their significant differences. Finally, we deliver a summary based on recent advancements in the therapeutic capability of CAR-T and CAR-NK cells in treating breast cancer.

摘要

尽管在手术、化疗、放疗、内分泌治疗和分子靶向治疗等常规治疗方面取得了重大进展,但乳腺癌仍是女性癌症死亡的主要原因。目前,嵌合抗原受体(CAR)靶向免疫细胞疗法作为一种创新的免疫治疗方法,通过诱导表达肿瘤相关抗原的肿瘤细胞的细胞毒性活性,改善了乳腺癌患者的生存率。作为适应性免疫的重要组成部分,T 细胞和 NK 细胞作为主要的先天免疫细胞,是 CAR 工程治疗实体恶性肿瘤的两种重要候选细胞类型。然而,NK 细胞和 T 细胞之间的生物学差异导致了癌症免疫治疗结果的不同。同样,通过 CAR 靶向免疫细胞实现最佳的乳腺癌切除需要检测安全的靶抗原,改善 CAR 结构以实现理想的免疫细胞功能,促进 CAR 靶向免疫细胞向肿瘤微环境(TME)的过滤,以及提高这些工程化细胞在免疫抑制性 TME 中持续存在和保留的能力。

这篇综述简要概述了乳腺癌的发病机制及其恶劣的 TME。我们重点介绍了 CAR-T 和 CAR-NK 细胞,并讨论了它们的显著差异。最后,我们根据 CAR-T 和 CAR-NK 细胞在治疗乳腺癌方面的治疗能力的最新进展进行了总结。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82b2/9344815/4d5389aaede1/JCMM-26-4137-g001.jpg

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