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免疫疗法和免疫工程在乳腺癌中的应用: CAR-T 细胞疗法的进展、挑战与展望的全面分析。

Immunotherapy and immunoengineering for breast cancer; a comprehensive insight into CAR-T cell therapy advancements, challenges and prospects.

机构信息

Department of Tissue Engineering, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Cell Oncol (Dordr). 2022 Oct;45(5):755-777. doi: 10.1007/s13402-022-00700-w. Epub 2022 Aug 9.


DOI:10.1007/s13402-022-00700-w
PMID:35943716
Abstract

BACKGROUND: Breast cancer (BC) is a highly prevalent solid cancer with a high-rise infiltration of immune cells, turning it into a significant candidate for tumor-specific immunotherapies. Chimeric antigen receptor (CAR)-T cells are emerging as immunotherapeutic tools with genetically engineered receptors to efficiently recognize and attack tumor cells that express specific target antigens. Technological advancements in CAR design have provided five generations of CAR-T cells applicable to a wide range of cancer patients while boosting CAR-T cell therapy safety. However, CAR-T cell therapy is ineffective against breast cancer because of the loss of specified antigens, the immunosuppressive nature of the tumor and CAR-T cell-induced toxicities. Next-generation CAR-T cells actively pass through the tumor vascular barriers, persist for extended periods and disrupt the tumor microenvironment (TME) to block immune escape. CONCLUSION: CAR-T cell therapy embodies advanced immunotherapy for BC, but further pre-clinical and clinical assessments are recommended to achieve maximized efficiency and safety.

摘要

背景:乳腺癌(BC)是一种高发的实体瘤,免疫细胞浸润度高,使其成为肿瘤特异性免疫治疗的重要候选者。嵌合抗原受体(CAR)-T 细胞作为免疫治疗工具不断涌现,其通过基因工程受体来有效识别和攻击表达特定靶抗原的肿瘤细胞。CAR 设计的技术进步提供了五代适用于广泛癌症患者的 CAR-T 细胞,同时提高了 CAR-T 细胞治疗的安全性。然而,由于特定抗原的丢失、肿瘤的免疫抑制性质以及 CAR-T 细胞诱导的毒性,CAR-T 细胞疗法对乳腺癌无效。下一代 CAR-T 细胞能够主动穿透肿瘤血管屏障,持续存在较长时间,并破坏肿瘤微环境(TME)以阻止免疫逃逸。

结论:CAR-T 细胞疗法体现了针对 BC 的先进免疫疗法,但需要进一步的临床前和临床评估,以实现最大的效率和安全性。

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Immunotherapy and immunoengineering for breast cancer; a comprehensive insight into CAR-T cell therapy advancements, challenges and prospects.

Cell Oncol (Dordr). 2022-10

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本文引用的文献

[1]
Extracellular matrix modulates T cell clearance of malignant cells in vitro.

Biomaterials. 2022-3

[2]
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Cancer Lett. 2022-1-1

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ALDH1A1 Activity in Tumor-Initiating Cells Remodels Myeloid-Derived Suppressor Cells to Promote Breast Cancer Progression.

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Tenascin-C immobilizes infiltrating T lymphocytes through CXCL12 promoting breast cancer progression.

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Macrophage Biology and Mechanisms of Immune Suppression in Breast Cancer.

Front Immunol. 2021

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Improving therapeutic potential of non-viral minimized DNA vectors.

Cell Gene Ther Insights. 2020-11

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