{"title":"通过调整抗体比例,增强抗 CD3/CD28 磁珠对 T 细胞的激活作用。","authors":"Yinuo Chen, Rui Zhao, Qi Fan, Mengmeng Liu, Yonglin Huang, Guoqing Shi","doi":"10.1002/iub.2898","DOIUrl":null,"url":null,"abstract":"<p>The utilization of anti-CD3/CD28 magnetic beads for T cell expansion in vitro has been investigated for adoptive cell transfer therapy. However, the impact of the CD3/CD28 antibody ratio on T cell differentiation and function remains incompletely elucidated. This study seeks to address this knowledge gap. To begin with, CD3 antibodies with a relatively low avidity for Jurkat cells (Kd = 13.55 nM) and CD28 antibodies with a relatively high avidity (Kd = 5.79 nM) were prepared. Afterwards, anti-CD3/CD28 antibodies with different mass ratios were attached to magnetic beads to examine the impacts of different antibody ratios on T cell capture, and proliferation. The research demonstrated that the most significant expansion of T cells was stimulated by the anti-CD3/CD28 magnetic beads with a mass ratio of 2:1 for CD3 antibodies and CD28 antibodies. Moreover, CD25 and PD1 expression of expanded T cells increased and then decreased, with lower CD25 and PD1 expression in the later stages of expansion indicating that T cells were not depleted. These T cells, which are massively expanded in vitro and have excellent expansion potential, can be infused back into the patient to treat tumor patients. This study shows that altering the ratio of anti-CD3/CD28 antibodies can control the strength of T cell stimulation, thereby leading to the improvement of T cell activation. This discovery can be utilized as a guide for the creation of other T cell stimulation approaches, which is beneficial for the further development of tumor immunotherapy technology.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 12","pages":"1175-1185"},"PeriodicalIF":3.7000,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhancing the activation of T cells through anti-CD3/CD28 magnetic beads by adjusting the antibody ratio\",\"authors\":\"Yinuo Chen, Rui Zhao, Qi Fan, Mengmeng Liu, Yonglin Huang, Guoqing Shi\",\"doi\":\"10.1002/iub.2898\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The utilization of anti-CD3/CD28 magnetic beads for T cell expansion in vitro has been investigated for adoptive cell transfer therapy. However, the impact of the CD3/CD28 antibody ratio on T cell differentiation and function remains incompletely elucidated. This study seeks to address this knowledge gap. To begin with, CD3 antibodies with a relatively low avidity for Jurkat cells (Kd = 13.55 nM) and CD28 antibodies with a relatively high avidity (Kd = 5.79 nM) were prepared. Afterwards, anti-CD3/CD28 antibodies with different mass ratios were attached to magnetic beads to examine the impacts of different antibody ratios on T cell capture, and proliferation. The research demonstrated that the most significant expansion of T cells was stimulated by the anti-CD3/CD28 magnetic beads with a mass ratio of 2:1 for CD3 antibodies and CD28 antibodies. Moreover, CD25 and PD1 expression of expanded T cells increased and then decreased, with lower CD25 and PD1 expression in the later stages of expansion indicating that T cells were not depleted. These T cells, which are massively expanded in vitro and have excellent expansion potential, can be infused back into the patient to treat tumor patients. This study shows that altering the ratio of anti-CD3/CD28 antibodies can control the strength of T cell stimulation, thereby leading to the improvement of T cell activation. This discovery can be utilized as a guide for the creation of other T cell stimulation approaches, which is beneficial for the further development of tumor immunotherapy technology.</p>\",\"PeriodicalId\":14728,\"journal\":{\"name\":\"IUBMB Life\",\"volume\":\"76 12\",\"pages\":\"1175-1185\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"IUBMB Life\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/iub.2898\",\"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":"IUBMB Life","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/iub.2898","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}
引用次数: 0
摘要
在体外利用抗 CD3/CD28 磁珠扩增 T 细胞用于采纳性细胞转移疗法的研究已经展开。然而,CD3/CD28 抗体比例对 T 细胞分化和功能的影响仍未完全阐明。本研究试图填补这一知识空白。首先,制备了对 Jurkat 细胞具有较低亲和力(Kd = 13.55 nM)的 CD3 抗体和具有较高亲和力(Kd = 5.79 nM)的 CD28 抗体。然后,将不同质量比的抗 CD3/CD28 抗体附着在磁珠上,研究不同抗体比对 T 细胞捕获和增殖的影响。研究表明,CD3 抗体和 CD28 抗体质量比为 2:1 的抗 CD3/CD28 磁珠对 T 细胞扩增的刺激最为明显。此外,扩增的 T 细胞的 CD25 和 PD1 表达量先升高后降低,扩增后期 CD25 和 PD1 表达量降低,表明 T 细胞未被耗尽。这些在体外大规模扩增的 T 细胞具有极好的扩增潜力,可以回输到患者体内治疗肿瘤患者。这项研究表明,改变抗 CD3/CD28 抗体的比例可以控制 T 细胞刺激的强度,从而改善 T 细胞的活化。这一发现可作为创建其他 T 细胞刺激方法的指南,有利于肿瘤免疫疗法技术的进一步发展。
Enhancing the activation of T cells through anti-CD3/CD28 magnetic beads by adjusting the antibody ratio
The utilization of anti-CD3/CD28 magnetic beads for T cell expansion in vitro has been investigated for adoptive cell transfer therapy. However, the impact of the CD3/CD28 antibody ratio on T cell differentiation and function remains incompletely elucidated. This study seeks to address this knowledge gap. To begin with, CD3 antibodies with a relatively low avidity for Jurkat cells (Kd = 13.55 nM) and CD28 antibodies with a relatively high avidity (Kd = 5.79 nM) were prepared. Afterwards, anti-CD3/CD28 antibodies with different mass ratios were attached to magnetic beads to examine the impacts of different antibody ratios on T cell capture, and proliferation. The research demonstrated that the most significant expansion of T cells was stimulated by the anti-CD3/CD28 magnetic beads with a mass ratio of 2:1 for CD3 antibodies and CD28 antibodies. Moreover, CD25 and PD1 expression of expanded T cells increased and then decreased, with lower CD25 and PD1 expression in the later stages of expansion indicating that T cells were not depleted. These T cells, which are massively expanded in vitro and have excellent expansion potential, can be infused back into the patient to treat tumor patients. This study shows that altering the ratio of anti-CD3/CD28 antibodies can control the strength of T cell stimulation, thereby leading to the improvement of T cell activation. This discovery can be utilized as a guide for the creation of other T cell stimulation approaches, which is beneficial for the further development of tumor immunotherapy technology.
期刊介绍:
IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.