Maher John, Davies David M
CAR Mechanics Group, Guy's Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, Great Maze Pond, London SE1 9RT, UK.
Department of Immunology, Eastbourne Hospital, Kings Drive, Eastbourne BN21 2UD, UK.
Biology (Basel). 2023 Feb 10;12(2):287. doi: 10.3390/biology12020287.
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.
使用嵌合抗原受体（CAR）工程化免疫细胞进行免疫治疗已经改变了某些血液系统癌症的治疗方式。然而，事实证明，使用这种新兴的治疗方式来控制实体瘤要困难得多。在本综述中，我们调查了基于CAR的实体瘤免疫治疗的临床影响，重点关注一系列疾病适应症中的特定靶点。在众多已成为非临床CAR T细胞研究对象的候选靶点中，有30个靶点的研究有临床数据。在此，我们梳理了这一临床经验，强调了免疫原性和脱靶毒性等挑战，这一问题在某些情况下既出乎意料又具有毁灭性。我们还总结了如何通过局部给药和重复给药来提高疗效和安全性。最后，我们思考了如何利用新兴的装甲系统和多靶点CAR方法来增强肿瘤靶向性，并更好地区分健康细胞和转化细胞类型。
