Chan Ler Yie, Dass Sylvia Annabel, Tye Gee Jun, Imran Siti A M, Wan Kamarul Zaman Wan Safwani, Nordin Fazlina
Centre for Tissue Engineering and Regenerative Medicine (CTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia.
INTEC Education College, Jalan Senangin Satu 17/2A, Seksyen 17, Shah Alam 40200, Malaysia.
Biomedicines. 2022 Mar 30;10(4):804. doi: 10.3390/biomedicines10040804.
The chimeric antigen receptor (CAR) plays a dynamic role in targeting tumour-associated antigens in cancer cells. This novel therapeutic discovery combines fragments of monoclonal antibodies with the signalling and co-stimulatory domains that have been modified to its current fourth generation. CAR has been widely implemented in T-cells and natural killer (NK) cells immunotherapy. The significant advancement in CAR technology is evident based on numerous ongoing clinical trials on CAR-T/-NK cells and successful CAR-related products such as Kymriah (Novartis) and Yescarta (Kite Pharma, Gilead). Another important cell-based therapy is the engineering of mesenchymal stem cells (MSC). Researchers have been exploring MSCs and their innate homing abilities to tumour sites and secretion cytokines that bridge both CAR and MSC technologies as a therapeutic agent. This combination allows for both therapies to overcome each one's flaw as an immunotherapy intervention. Herein, we have provided a concise review on the background of CAR and its applications in different cancers, as well as MSCs' unique ability as delivery vectors for cancer therapy and the possibility of enhancing the CAR-immune cells' activity. Hence, we have highlighted throughout this review the synergistic effects of both interventions.
嵌合抗原受体(CAR)在靶向癌细胞中的肿瘤相关抗原方面发挥着动态作用。这一新颖的治疗发现将单克隆抗体片段与已被修饰至当前第四代的信号传导和共刺激结构域结合在一起。CAR已广泛应用于T细胞和自然杀伤(NK)细胞免疫疗法。基于众多正在进行的CAR-T/NK细胞临床试验以及成功的CAR相关产品,如Kymriah(诺华)和Yescarta(吉利德旗下凯特制药公司),CAR技术取得了显著进展。另一种重要的基于细胞的疗法是间充质干细胞(MSC)的工程改造。研究人员一直在探索MSC及其向肿瘤部位的天然归巢能力,以及作为一种治疗剂连接CAR和MSC技术的分泌细胞因子。这种组合使两种疗法都能克服各自作为免疫治疗干预手段的缺陷。在此,我们简要综述了CAR的背景及其在不同癌症中的应用,以及MSC作为癌症治疗递送载体的独特能力,以及增强CAR免疫细胞活性的可能性。因此,我们在本综述中强调了这两种干预措施的协同效应。