Wang Shuhang, Chen Kun, Jiang Yale, Zhao Guo, Wang Caie, Fang Hong, Tang Qiyu, Sun Chao, Zhang Liang, Wu Haiyang, Zhang Li-Feng, Li Ning
Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Guizhou Provincial People's Hospital, Guiyang, China.
Drug Discov Today. 2023 Feb;28(2):103436. doi: 10.1016/j.drudis.2022.103436. Epub 2022 Nov 10.
Natural killer (NK) cell therapy is emerging as a cancer treatment. NK cells are innate cytotoxic lymphocytes that act as first-line responders to kill target cells without prior encounters. NK cells recognize cancer cells, virus-infected cells, and other types of stressed cell through a reservoir of germline-encoded receptors. NK cells are safe for allogeneic applications. Therefore, they are the ideal off-the-shelf cell, which overcome the low efficiency issue caused by the patient-by-patient nature of autologous cell therapy. Unlike T cells, NK cells cannot form a strong immune memory; therefore, they suffer from short in vivo persistence. However, different from T cells, NK cells have a reservoir of innate immune receptors targeting a variety of malignant cells. In addition, they can utilize antibody guidance in target recognition. With suitable engineering, NK cells can function as universal anticancer drugs that are not restricted to HLA and cancer types, which will benefit the large cohort of patients with rare cancer types and patients with no convenient drug targets for precision and personalized medicine. Here, we summarize and discuss the designs of current anticancer NK cell therapies.
自然杀伤（NK）细胞疗法正在成为一种癌症治疗方法。NK细胞是先天性细胞毒性淋巴细胞，作为一线反应者，无需预先接触就能杀死靶细胞。NK细胞通过一系列种系编码的受体识别癌细胞、病毒感染细胞和其他类型的应激细胞。NK细胞用于同种异体治疗是安全的。因此，它们是理想的现成可用细胞，克服了自体细胞疗法因逐个患者特性而导致的效率低下问题。与T细胞不同，NK细胞不能形成强大的免疫记忆；因此，它们在体内的持久性较短。然而，与T细胞不同的是，NK细胞拥有针对多种恶性细胞的先天性免疫受体库。此外，它们可以在靶标识别中利用抗体引导。通过适当的工程改造，NK细胞可以作为不受HLA和癌症类型限制的通用抗癌药物，这将使大量罕见癌症类型患者以及没有方便的精准和个性化药物靶点的患者受益。在此，我们总结并讨论当前抗癌NK细胞疗法的设计。
