{"title":"通过调节细胞内氧化还原状态增强 CAR-NK-92 细胞的体内外扩增","authors":"","doi":"10.1016/j.procbio.2024.09.010","DOIUrl":null,"url":null,"abstract":"<div><p>Chimeric antigen receptor-Natural Killer-92 (CAR-NK-92) cell therapy has broad prospects as an effective cellular immunotherapy. Efficient CAR-NK-92 cell expansion <em>ex vivo</em> is crucial for its development and wide use. Unlike NK-92 cells, CAR-NK-92 cells need to maintain the stability of CAR expression during culture, besides keeping cell function. This work compared the growth and metabolism between NK-92 cells and CAR-NK-92 cells and found that the expansion efficiency of CAR-NK-92 cells was significantly lower than that of NK-92 cells. Meanwhile, the amino acid metabolism related to reducing agent production in CAR-NK-92 cells was weaker than in NK-92 cells, resulting in higher intracellular oxidation levels. The antioxidant N-acetylcysteine (NAC) was used to regulate the intracellular redox status of CAR-NK-92 cells. Under 1 mM NAC, the intracellular reactive oxygen species (ROS) level of CAR-NK-92 cells was down-regulated, and the cell expansion ability was improved. Furthermore, the addition of NAC has increased the levels of GSH and NADPH in CAR-NK-92 cells, elevated GSH/GSSG ratio and NADPH/NADP<sup>+</sup> ratio, enhanced the antioxidant capacity and mitochondrial function of cells, and promoted cell expansion. This study aims to promote CAR-NK-92 cell expansion <em>ex vivo</em> by regulating intracellular redox levels to facilitate its clinical application.</p></div>","PeriodicalId":20811,"journal":{"name":"Process Biochemistry","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"To enhance the ex vivo expansion of CAR-NK-92 cells by regulating intracellular redox status\",\"authors\":\"\",\"doi\":\"10.1016/j.procbio.2024.09.010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Chimeric antigen receptor-Natural Killer-92 (CAR-NK-92) cell therapy has broad prospects as an effective cellular immunotherapy. Efficient CAR-NK-92 cell expansion <em>ex vivo</em> is crucial for its development and wide use. Unlike NK-92 cells, CAR-NK-92 cells need to maintain the stability of CAR expression during culture, besides keeping cell function. This work compared the growth and metabolism between NK-92 cells and CAR-NK-92 cells and found that the expansion efficiency of CAR-NK-92 cells was significantly lower than that of NK-92 cells. Meanwhile, the amino acid metabolism related to reducing agent production in CAR-NK-92 cells was weaker than in NK-92 cells, resulting in higher intracellular oxidation levels. The antioxidant N-acetylcysteine (NAC) was used to regulate the intracellular redox status of CAR-NK-92 cells. Under 1 mM NAC, the intracellular reactive oxygen species (ROS) level of CAR-NK-92 cells was down-regulated, and the cell expansion ability was improved. Furthermore, the addition of NAC has increased the levels of GSH and NADPH in CAR-NK-92 cells, elevated GSH/GSSG ratio and NADPH/NADP<sup>+</sup> ratio, enhanced the antioxidant capacity and mitochondrial function of cells, and promoted cell expansion. This study aims to promote CAR-NK-92 cell expansion <em>ex vivo</em> by regulating intracellular redox levels to facilitate its clinical application.</p></div>\",\"PeriodicalId\":20811,\"journal\":{\"name\":\"Process Biochemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Process Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1359511324003076\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Process Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1359511324003076","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
To enhance the ex vivo expansion of CAR-NK-92 cells by regulating intracellular redox status
Chimeric antigen receptor-Natural Killer-92 (CAR-NK-92) cell therapy has broad prospects as an effective cellular immunotherapy. Efficient CAR-NK-92 cell expansion ex vivo is crucial for its development and wide use. Unlike NK-92 cells, CAR-NK-92 cells need to maintain the stability of CAR expression during culture, besides keeping cell function. This work compared the growth and metabolism between NK-92 cells and CAR-NK-92 cells and found that the expansion efficiency of CAR-NK-92 cells was significantly lower than that of NK-92 cells. Meanwhile, the amino acid metabolism related to reducing agent production in CAR-NK-92 cells was weaker than in NK-92 cells, resulting in higher intracellular oxidation levels. The antioxidant N-acetylcysteine (NAC) was used to regulate the intracellular redox status of CAR-NK-92 cells. Under 1 mM NAC, the intracellular reactive oxygen species (ROS) level of CAR-NK-92 cells was down-regulated, and the cell expansion ability was improved. Furthermore, the addition of NAC has increased the levels of GSH and NADPH in CAR-NK-92 cells, elevated GSH/GSSG ratio and NADPH/NADP+ ratio, enhanced the antioxidant capacity and mitochondrial function of cells, and promoted cell expansion. This study aims to promote CAR-NK-92 cell expansion ex vivo by regulating intracellular redox levels to facilitate its clinical application.
期刊介绍:
Process Biochemistry is an application-orientated research journal devoted to reporting advances with originality and novelty, in the science and technology of the processes involving bioactive molecules and living organisms. These processes concern the production of useful metabolites or materials, or the removal of toxic compounds using tools and methods of current biology and engineering. Its main areas of interest include novel bioprocesses and enabling technologies (such as nanobiotechnology, tissue engineering, directed evolution, metabolic engineering, systems biology, and synthetic biology) applicable in food (nutraceutical), healthcare (medical, pharmaceutical, cosmetic), energy (biofuels), environmental, and biorefinery industries and their underlying biological and engineering principles.