CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
实体瘤 CAR-T 细胞治疗取得突破的障碍
英文原题：Hurdles to breakthrough in CAR T cell therapy of solid tumors.
查看英文原题
Hurdles to breakthrough in CAR T cell therapy of solid tumors.
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中文摘要
经基因工程改造表达嵌合抗原受体（CAR）的自体T细胞已显示良好结局，并成为血液系统恶性肿瘤、尤其B细胞恶性肿瘤的新型治愈选择。值得注意的是，T细胞转导单克隆抗体抗原识别结构域构成的CAR后，可保留其细胞毒特性，而且不依赖主要组织相容性复合体（MHC）。尽管具有获益，目前CAR-T 细胞疗法用于实体瘤仍面临诸多挑战，包括免疫抑制性肿瘤微环境（TME）、肿瘤抗原异质性、基质屏障、肿瘤可及性，以及靶向肿瘤外组织毒性和细胞因子释放综合征（CRS）等问题。本文重点介绍限制CAR-T 细胞治疗实体瘤疗效的并发问题，并综述为克服这些障碍、改善输注T细胞表现而提出的策略。
展开英文摘要原文
Autologous T cells genetically engineered to express chimeric antigen receptor (CAR) have shown promising outcomes and emerged as a new curative option for hematological malignancy, especially malignant neoplasm of B cells.
Notably, when T cells are transduced with CAR constructs, composed of the antigen recognition domain of monoclonal antibodies, they retain their cytotoxic properties in a major histocompatibility complex (MHC)-independent manner.
Despite its beneficial effect, the current CAR T cell therapy approach faces myriad challenges in solid tumors, including immunosuppressive tumor microenvironment (TME), tumor antigen heterogeneity, stromal impediment, and tumor accessibility, as well as tribulations such as on-target/off-tumor toxicity and cytokine release syndrome (CRS).
Herein, we highlight the complications that hamper the effectiveness of CAR T cells in solid tumors and the strategies that have been recommended to overcome these hurdles and improve infused T cell performance.
论文信息
- 作者
- Marofi F、Achmad H、Bokov D、Abdelbasset WK、Alsadoon Z、Chupradit S、Suksatan W、Shariatzadeh S
- 第一作者单位
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran.Iran
- 通讯作者单位
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran. farhadmotavallikhiavi@gmail.com.Iran
- 文献类型
- 综述 · 已撤稿
- 期刊
- Stem cell research & therapy2022 Apr 1
- 原文标识
- PubMed 35365241 · DOI 10.1186/s13287-022-02819-x
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