Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115, USA.
EBioMedicine. 2020 Sep;59:102975. doi: 10.1016/j.ebiom.2020.102975. Epub 2020 Aug 24.
Natural Killer (NK) cells and CD8 cytotoxic T cells are two types of immune cells that can kill target cells through similar cytotoxic mechanisms. With the remarkable success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells for treating haematological malignancies, there is a rapid growing interest in developing CAR-engineered NK (CAR-NK) cells for cancer therapy. Compared to CAR-T cells, CAR-NK cells could offer some significant advantages, including: (1) better safety, such as a lack or minimal cytokine release syndrome and neurotoxicity in autologous setting and graft-versus-host disease in allogenic setting, (2) multiple mechanisms for activating cytotoxic activity, and (3) high feasibility for 'off-the-shelf' manufacturing. CAR-NK cells could be engineered to target diverse antigens, enhance proliferation and persistence in vivo, increase infiltration into solid tumours, overcome resistant tumour microenvironment, and ultimately achieve an effective anti-tumour response. In this review, we focus on recent progress in genetic engineering and clinical application of CAR-NK cells, and discuss current challenges and future promise of CAR-NK cells as a novel cellular immunotherapy in cancer.
自然杀伤 (NK) 细胞和 CD8 细胞毒性 T 细胞是两种能够通过相似的细胞毒性机制杀死靶细胞的免疫细胞。嵌合抗原受体 (CAR)-修饰的 T (CAR-T) 细胞在治疗血液恶性肿瘤方面取得了显著成功，因此人们对开发用于癌症治疗的 CAR 修饰的 NK (CAR-NK) 细胞产生了浓厚的兴趣。与 CAR-T 细胞相比，CAR-NK 细胞可能具有一些显著优势，包括：(1) 更好的安全性，例如在自体环境中缺乏或极少出现细胞因子释放综合征和神经毒性，在同种异体环境中则无移植物抗宿主病；(2) 激活细胞毒性活性的多种机制；(3) “现货”制造的高可行性。可以对 CAR-NK 细胞进行工程改造以靶向多种抗原，增强其在体内的增殖和持久性，增加对实体瘤的浸润，克服耐药性肿瘤微环境，最终实现有效的抗肿瘤反应。在这篇综述中，我们重点介绍了 CAR-NK 细胞的基因工程和临床应用的最新进展，并讨论了 CAR-NK 细胞作为一种新型细胞免疫疗法在癌症治疗中的当前挑战和未来前景。
