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CAR-T 细胞:治疗脑肿瘤及其他疾病的工程化免疫细胞

英文原题:CAR T cells: engineered immune cells to treat brain cancers and beyond.

PubMed 2023/01/31(内容时间) Mol Cancer Q1 · IF 42.2(JCR 2025)

研究概要

恶性脑肿瘤属于治疗难度最大的恶性肿瘤类型。

中文摘要

恶性脑肿瘤是最难治疗的恶性肿瘤之一。目前常见治疗方案为手术后接受放疗和/或化疗,但患者中位生存情况不佳。近期多种肿瘤免疫治疗的发展令人乐观,提示免疫策略或可帮助脑癌患者。嵌合抗原受体(CAR)T细胞利用抗体或受体配体的肿瘤靶向特异性,引导T细胞发挥细胞溶解功能。研究者已发现多种免疫疗法潜在靶分子,包括但不限于EGFRvIII、IL13Rα2和HER2。血液系统恶性肿瘤患者接受CAR T细胞治疗取得显著临床反应,引发了将该方法用于实体瘤治疗的兴趣。迄今研究结果支持CD19靶向CAR T细胞具有极高临床反应率;脑肿瘤早期临床研究显示其安全性和疾病修饰活性证据,并有望进一步进步以最终惠及患者。然而,若干变异因素似乎减缓了CAR T细胞治疗脑癌的进展。本综述全面分析CAR T细胞治疗脑癌的前景,包括设计和递送考量、当前临床与临床前研究进展、遇到的问题及潜在解决方案。

展开英文摘要原文

Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential targets for immunotherapy-based targeting, including but not limited to EGFRvIII, IL13R 2, and HER2. The outstanding clinical responses to CAR T cell-based treatments in patients with hematological malignancies have generated interest in using this approach to treat solid tumors. Research results to date support the astounding clinical response rates of CD19-targeted CAR T cells, early clinical experiences in brain tumors demonstrating safety and evidence for disease-modifying activity, and the promise for further advances to ultimately assist patients clinically. However, several variable factors seem to slow down the progress rate regarding treating brain cancers utilizing CAR T cells. The current study offers a thorough analysis of CAR T cells' promise in treating brain cancer, including design and delivery considerations, current strides in clinical and preclinical research, issues encountered, and potential solutions.

论文信息

作者
Huang Z、Dewanjee S、Chakraborty P、Jha NK、Dey A、Gangopadhyay M、Chen XY、Wang J
第一作者单位
Department of Hematology, Ganzhou Key Laboratory of Hematology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.China
通讯作者单位
Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida, Uttar Pradesh, 201310, India. saurabh.jha@sharda.ac.in.India
文献类型
非美国政府资助研究 · 综述
期刊
Molecular cancer2023 Jan 31
原文标识
PubMed 36721153 · DOI 10.1186/s12943-022-01712-8