T细胞受体基因修饰在过继免疫治疗中的应用  

Application of T cell receptor gene modification in adoptive immunotherapy

作　　者：邰文[1] 刘东博[1] 吴疆[1] 潘明佳[1] 陈常青[1] 

机构地区：[1]天津药物研究院,天津300193

出　　处：《药物评价研究》2011年第2期105-109,共5页Drug Evaluation Research

摘　　要：T细胞过继性转移可以增强免疫系统介导的对肿瘤细胞的消除,是近年来获得较高关注的一种特异性、无毒性的癌症新疗法,此方法对于治疗血液性和实体恶性肿瘤具有一定效果。对T细胞进行基因修饰能够增强其免疫能力,保持T细胞的持久活性,同时也可以克服肿瘤自身的免疫逃避机制,潜在提高免疫治疗应用于多种肿瘤疾病的成功率。在T细胞过继转移中,T细胞受体(TCR)基因转移作为一种发展迅速的免疫治疗方法,可以在体外产生大量的具有已知抗原特异性和功能亲和性的T细胞,应用于病毒感染或病毒相关恶性肿瘤的过继细胞免疫治疗。TCR基因转移利用逆转录病毒或慢病毒作为载体,其中包含了从所需抗体特异性T细胞群中克隆得到的TCR-α和TCR-β链基因序列,然后应用TCR编码载体转导体外的原始T细胞。为产生带有所需功能特异性的转导T细胞,引入的TCR-α和TCR-β链必须形成异源二聚体,与CD3复合体结合从而在T细胞表面稳定表达。T cell adoptive transfer could enhance immune-mediated elimination of tumor cells with high concerns for providing a specific and non-toxic cancer therapy,.This approach has been effective in treating some hematologic and solid malignancies.Moreover,genetic modification of T cells could improve their immunopotency,maintain their persistence,and overcome the tumor immune evasion mechanisms as well,so as to potentially increase the achievement rate of immunotherapy in a wide range of tumors.In T cell adoptive transfer,T cell receptor （TCR） gene transfer,a rapid developing strategy of immunotherapy,can generate a number of T cells with a given antigen-specificity and functional avidity in vitro and is used to treat viral infectious diseases and virus-associated malignancies and caner.TCR gene transfer utilizes retrovirus or lentivirus as vectors which contain gene sequences of the TCR-α and β chains.TCR-α and -β chains were cloned from a T-cell population with the desired antigen specificity.Then the TCR encoding vector is used to transduce primary T cells in vitro.To generate a transduced T cell with the disired functional specificity,the introduced TCR-α and -β chains must form a heterodimer and combine with the CD3 complex in order to be stably expressed at the T-cell surface.

关 键 词：T细胞 基因修饰 T细胞受体 基因转移 过继免疫治疗 

分 类 号：R73-362[医药卫生—肿瘤]