基于NK细胞受体的CAR-T细胞疗法在实体瘤治疗中的研究进展

摘要/Abstract

摘要： 嵌合抗原受体（CAR）T细胞免疫疗法属于过继性细胞免疫治疗，通过将CAR的特异性与T细胞免疫作用相结合，再经过特异性识别对恶性肿瘤细胞进行杀伤。NK细胞是免疫系统中发挥细胞毒作用最重要的细胞之一，主要依赖于其细胞膜表面的激活性受体和抑制性受体参与天然免疫和适应性免疫。基于NK细胞受体的CAR-T细胞可以识别表达其配体的病毒感染或者突变恶性细胞，具有多靶点、广谱性、不易耐药的特点，可以用于多种血液系统及实体性恶性肿瘤的治疗，应用前景良好。本研究梳理了CAR-T细胞疗法的原理及其局限性，以及基于NK细胞受体的CAR-T细胞疗法，分析了实体瘤中CAR-T细胞细胞免疫治疗的主要困难及其解决策略，重点探讨了NK细胞激活性受体NKG2D、NKp30及其配体分别在肿瘤治疗中的研究和应用，以期为基于NK细胞受体的CAR-T细胞疗法治疗实体瘤提供借鉴。

关键词: font-size:medium, ">细胞治疗；NK细胞受体；实体瘤；NKG2D；NKp30

Abstract: Chimeric antigen receptor T-cell immunotherapy (CAR) is a kind of adoptive cellular immunotherapy that combines the specificity of CAR with T-cell immunity， then through the specific recognition of malignant tumor cells to kill. NK cells are one of the most important cytotoxic cells in the immune system， which mainly depend on the active and inhibitory receptors on their cell membrane surface to participate in innate and adaptive immunity.NK-cell receptor-based CAR-T cells can recognize the viral infection or mutant malignant cells expressing their ligands， which has the characteristics of multi-target， broad-spectrum and difficult to drug resistance， it can be used in the treatment of many kinds of hematological system and solid malignant tumors.This study reviewed the principles and limitations of CAR-T-cell therapy and NK-cell receptor-based CAR-T-cell therapy， and analyzed the main challenges and strategies of CAR-T-cell immunotherapy in solid tumors， the research and application of NK cell receptor NKG2D， NKP30 and their ligands in tumor therapy were discussed in order to provide references for NK cell receptor-based CAR-T cell therapy for solid tumors.

Key words: font-size:medium, ">Cell therapy； NK cell receptor； Solid tumor； NKG2D； NKP30

中图分类号:

张玉莹, 林怡婷, 王首占, 初明, 王月丹. 基于NK细胞受体的CAR-T细胞疗法在实体瘤治疗中的研究进展[J]. 中国医药导刊, 2022, 24(11): 1055-1061.

ZHANG Yuying, LIN Yiting, WANG Shouzhan, CHU Ming, WANG Yuedan. Research Progress of NK Cell Receptor-Based CAR-T Cell Therapy in the Treatment of Solid Tumors[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2022, 24(11): 1055-1061.

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