[關(guān)鍵詞]
[摘要]
T細(xì)胞過繼性轉(zhuǎn)移可以增強(qiáng)免疫系統(tǒng)介導(dǎo)的對腫瘤細(xì)胞的消除,是近年來獲得較高關(guān)注的一種特異性、無毒性的癌癥新療法,此方法對于治療血液性和實(shí)體惡性腫瘤具有一定效果。對T細(xì)胞進(jìn)行基因修飾能夠增強(qiáng)其免疫能力,保持T細(xì)胞的持久活性,同時也可以克服腫瘤自身的免疫逃避機(jī)制,潛在提高免疫治療應(yīng)用于多種腫瘤疾病的成功率。在T細(xì)胞過繼轉(zhuǎn)移中,T細(xì)胞受體(TCR)基因轉(zhuǎn)移作為一種發(fā)展迅速的免疫治療方法,可以在體外產(chǎn)生大量的具有已知抗原特異性和功能親和性的T細(xì)胞,應(yīng)用于病毒感染或病毒相關(guān)惡性腫瘤的過繼細(xì)胞免疫治療。TCR基因轉(zhuǎn)移利用逆轉(zhuǎn)錄病毒或慢病毒作為載體,其中包含了從所需抗體特異性T細(xì)胞群中克隆得到的TCR-α和TCR-β鏈基因序列,然后應(yīng)用TCR編碼載體轉(zhuǎn)導(dǎo)體外的原始T細(xì)胞。為產(chǎn)生帶有所需功能特異性的轉(zhuǎn)導(dǎo)T細(xì)胞,引入的TCR-α和TCR-β鏈必須形成異源二聚體,與CD3復(fù)合體結(jié)合從而在T細(xì)胞表面穩(wěn)定表達(dá)。
[Key word]
[Abstract]
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.
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