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用于实体瘤的嵌合抗原受体设计:克服障碍并为有效免疫治疗铺平道路。

CAR designs for solid tumors: overcoming hurdles and paving the way for effective immunotherapy.

作者信息

Cui Yuanbin, Luo Mintao, Gu Chuanyuan, He Yuxian, Yao Yao, Li Peng

机构信息

China-New Zealand Joint Laboratory of Biomedicine and Health, State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.

University of California San Diego, La Jolla, CA 92093-0021, USA.

出版信息

Biophys Rep. 2023 Oct 31;9(5):279-297. doi: 10.52601/bpr.2023.230020.

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized immunotherapy by modifying patients' immune cells genetically. By expressing CARs, these modified cells can specifically identify and eliminate tumor cells. The success of CAR-T therapy in hematological malignancies, such as leukemia and lymphoma, has been remarkable. Numerous studies have reported improved patient outcomes and increased survival rates. However, the application of CAR-T therapy in treating solid tumors faces significant challenges. Solid tumors possess complex microenvironments containing stromal cells, extracellular matrix components, and blood vessels. These factors can impede the infiltration and persistence of CAR-T cells within the tumor. Additionally, the lack of target antigens exclusively expressed on tumor cells raises concerns about off-target effects and potential toxicity. This review aims to discuss advancements achieved by CAR-T therapy in solid tumors and the clinical outcomes in the realm of solid tumors.

摘要

嵌合抗原受体T细胞(CAR-T)疗法通过对患者的免疫细胞进行基因改造,彻底改变了免疫疗法。通过表达嵌合抗原受体(CARs),这些经过改造的细胞能够特异性地识别并清除肿瘤细胞。CAR-T疗法在白血病和淋巴瘤等血液系统恶性肿瘤的治疗中取得了显著成功。大量研究报告显示患者预后得到改善,生存率提高。然而,CAR-T疗法在实体瘤治疗中的应用面临重大挑战。实体瘤拥有包含基质细胞、细胞外基质成分和血管的复杂微环境。这些因素会阻碍CAR-T细胞在肿瘤内的浸润和持久性。此外,缺乏仅在肿瘤细胞上表达的靶抗原引发了对脱靶效应和潜在毒性的担忧。本综述旨在探讨CAR-T疗法在实体瘤治疗中取得的进展以及实体瘤领域的临床疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a34c/10951476/42723b4c8cbc/br-9-5-279-1.jpg

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