Long-term phenotypic, functional and genetic stability of cancer-specific T-cell receptor (TCR) αβ genes transduced to CD8+ T cells
Long-term phenotypic, functional and genetic stability of cancer-specific T-cell receptor (TCR) αβ genes transduced to CD8+ T cells
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DOI：
10.1038/sj.gt.3303099
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发表时间：
2008-05-01
期刊：
影响因子：
5.1
通讯作者：
Shiku, H.
中科院分区：
文献类型：
--
作者：
Hiasa, A.;Hirayama, M.;Shiku, H.
在作为恶性疾病干预的过继性T细胞转移中，来源于CD 8（+）细胞毒性T淋巴细胞（CTL）克隆的T细胞受体（TCR）基因的逆转录病毒转移提供了产生大量具有相同抗原特异性的T细胞的机会。我们从对法师- A4（143-151）特异的人白细胞抗原（HLA）- A*2402限制性CTL克隆中克隆了TCR-α β基因。通过逆转录病毒转导，TCR-α β基因被转导至99.2%的非TCR表达SupT 1（一种人类T细胞系）和12.7-32.6%的多克隆激活的CD 8 + T细胞。正如预期的，TCR-α β基因修饰的CD 8（+）T细胞显示出响应于负载肽的T2- A* 2402和表达MAGE-A4和HLA-A*2402的肿瘤细胞系的细胞毒性活性和干扰素-γ产生。从TCR-α β基因转导的外周血单核细胞建立总共24个克隆，并且所有克隆都以转导的TCR依赖性方式起作用。将四个克隆在培养物中保持6个月以上用于详细分析。转导的TCR-α β基因在表型、功能和遗传上稳定维持。我们的研究结果表明，通过逆转录病毒转导的TCR转导的α β T细胞代表了长期过继性T细胞转移的有效和有前途的策略。
In adoptive T-cell transfer as an intervention for malignant diseases, retroviral transfer of T-cell receptor ( TCR) genes derived from CD8(+) cytotoxic T-lymphocyte ( CTL) clones provides an opportunity to generate a large number of T cells with the same antigen specificity. We cloned the TCR-alpha beta genes from a human leukocyte antigen ( HLA)- A*2402 restricted CTL clone specific for MAGE- A4(143-151). The TCR-alpha beta genes were transduced to 99.2% of non-TCR expressing SupT1, a human T-cell line, and to 12.7-32.6% of polyclonally activated CD8+ T cells by retroviral transduction. As expected, TCR-alpha beta gene- modified CD8(+) T cells showed cytotoxic activity and interferon-gamma production in response to peptide-loaded T2- A* 2402 and tumor cell lines expressing both MAGE-A4 and HLA-A*2402. A total of 24 clones were established from TCR-alpha beta gene-transduced peripheral blood mononuclear cells and all clones were functional on a transduced TCR-dependent manner. Four clones were kept in culture over 6 months for analyses in detail. The transduced TCR-alpha beta genes were stably maintained phenotypically, functionally and genetically. Our results indicate that TCR-transduced alpha beta T cells by retroviral transduction represent an efficient and promising strategy for adoptive T-cell transfer for long term.