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实体瘤的 CAR 免疫治疗——基于临床的靶抗原综述

英文原题:CAR Based Immunotherapy of Solid Tumours-A Clinically Based Review of Target Antigens.

查看英文原题

CAR Based Immunotherapy of Solid Tumours-A Clinically Based Review of Target Antigens.

PubMed 2023/02/10(内容时间) Biology (Basel) Q1 · IF 4.3(JCR 2025)

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中文摘要

采用CAR工程化免疫细胞的免疫疗法已改变部分血液系统恶性肿瘤的治疗。然而,这种新兴治疗方式对实体瘤的控制难度大得多。本综述概述实体瘤CAR免疫疗法的临床影响,重点介绍不同疾病适应证中的具体靶点。在众多接受非临床CAR-T 研究的候选靶点中,已有30个靶点的相关研究报告了临床数据。本文梳理这些临床经验,并强调免疫原性和靶向肿瘤外正常组织毒性等挑战;后者在某些情况下出乎意料且后果严重。我们还总结了采用局部递送和重复给药以增强疗效及安全性的尝试。最后,探讨新兴的增强型系统和多靶点CAR策略如何提高肿瘤可及性,并更好地区分健康细胞与恶性转化细胞。

展开英文摘要原文

Immunotherapy with CAR-engineered immune cells has transformed the management of selected haematological cancers.

However, solid tumours have proven much more difficult to control using this emerging therapeutic modality. In this review, we survey the clinical impact of solid tumour CAR-based immunotherapy, focusing on specific targets across a range of disease indications Among the many candidates which have been the subject of non-clinical CAR T-cell research, clinical data are available for studies involving 30 of these targets.

Here, we map out this clinical experience, highlighting challenges such as immunogenicity and on-target off-tumour toxicity, an issue that has been both unexpected and devastating in some cases.

We also summarise how regional delivery and repeated dosing have been used in an effort to enhance impact and safety.

Finally, we consider how emerging armouring systems and multi-targeted CAR approaches might be used to enhance tumour access and better enable discrimination between healthy and transformed cell types.

论文信息

作者
Maher J、Davies DM
第一作者单位
CAR Mechanics Group, Guy's Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, Great Maze Pond, London SE1 9RT, UK.United Kingdom
通讯作者单位
Leucid Bio Ltd., Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.United Kingdom
文献类型
综述
期刊
Biology2023 Feb 10
原文标识
PubMed 36829563 · DOI 10.3390/biology12020287