自然杀伤细胞免疫疗法在恶性肿瘤治疗中的研究进展

Progress of natural killer cell immunotherapy in the treatment of malignant tumors

自然杀伤细胞(Natural killer cell,NK)介导的免疫疗法是一种新的、安全的细胞治疗方法,临床已证实能够有效治疗多种恶性肿瘤。目前,NK细胞免疫疗法的研究主要集中在优化NK细胞的来源和增强NK细胞抗肿瘤活性两个方面。文章从NK细胞免疫疗法的发展、细胞来源及抗肿瘤活性等方面进行简述。NK细胞来源于骨髓,是除T、B细胞之外的第三大类淋巴细胞。目前用于治疗的NK细胞的来源主要有外周血和脐带血分离的NK细胞、NK细胞系和多能干细胞来源的NK细胞(Natural killer cells from pluripotent stem cells,PSC-NK);其中,PSC-NK作为NK细胞一种新的来源,具有数量充足和质量统一的特点,能够满足对癌症患者进行治疗的细胞数量需求,更符合临床治疗的要求。嵌合抗原受体联合的NK细胞(Chimeric antigen receptor modified natural killer cells,CAR-NK)比天然状态的NK细胞具有更强的特异性和细胞毒性,可进一步增强其抗肿瘤的活性。另外,通过基因工程技术改造NK细胞,避免在体内添加扩增NK细胞的外源性细胞因子,从而提高NK细胞的安全性和持久性,可有效推动NK细胞免疫疗法的临床应用。

Natural killer cell(NK)-mediated immunotherapy is a new and safe cell therapy that has been clinically proven to be effective in treating a variety of malignancies.Currently,research on NK cell immunotherapy has focused on optimizing the source of NK cells and enhancing the anti-tumor activity of NK cells.This article briefly reviews the development,cell source and antitumor activity of NK cell immunotherapy.NK cells are derived from bone marrow and are the third major type of lymphocytes besides T and B cells.The main sources of NK cells currently used for therapeutic purposes are NK cells for isolating peripheral blood and and cord blood,NK cell lines and NK cells from pluripotent stem cells(PSC-NK).Among them,PSC-NK,as a new source of NK cells,has the characteristics of sufficient quantity and uniform quality to meet the demand of cell quantity for the treatment of cancer patients,and is more in line with the requirements of clinical treatment.Chimeric antigen receptor modified natural killer cells(CAR-NK)have stronger specificity and cytotoxicity than NK cells in their natural state,which can further enhance their anti-tumor activity.In addition,the modification of NK cells by genetic engineering technology avoids the addition of exogenous cytokines to expand NK cells in vivo,improves the safety and durability of NK cells,and can effectively promote the clinical application of NK cell immunotherapy.