Coccoris Miriam, Swart Erwin, de Witte Moniek A, van Heijst Jeroen W J, Haanen John B A G, Schepers Koen, Schumacher Ton N M
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
J Immunol. 2008 May 15;180(10):6536-43. doi: 10.4049/jimmunol.180.10.6536.
To broaden the applicability of adoptive T cell therapy to cancer types for which tumor-specific T cells cannot routinely be isolated, an effort has been made to develop the transfer of tumor-specific TCR genes into autologous T cells as a novel immunotherapeutic approach. Although such TCR-modified T cells have been shown to react to Ag encounter and can be used to break tolerance to defined self-Ags, the persistence and capacity for renewed expansion of TCR-modified T cells has not been analyzed. To establish whether TCR-transduced T cells can provide recipients with long-term Ag-specific immune protection, we analyzed long-term function of TCR transduced T cells in mouse model systems. We demonstrate that polyclonal populations of T cells transduced with a class I restricted OVA-specific TCR are able to persist in vivo and respond upon re-encounter of cognate Ag as assessed by both proliferation and cytolytic capacity. These experiments indicate that TCR gene transfer can be used to generate long-term Ag-specific T cell responses and provide a useful model system to assess the factors that can promote high-level persistence of TCR-modified T cells.
为了拓宽过继性T细胞疗法对那些无法常规分离肿瘤特异性T细胞的癌症类型的适用性，人们已致力于开发将肿瘤特异性TCR基因转移至自体T细胞中的新型免疫治疗方法。尽管此类经TCR修饰的T细胞已被证明可对遇到的抗原作出反应，并可用于打破对特定自身抗原的耐受性，但尚未对经TCR修饰的T细胞的持久性和再次扩增能力进行分析。为了确定经TCR转导的T细胞是否能够为受体提供长期的抗原特异性免疫保护，我们在小鼠模型系统中分析了经TCR转导的T细胞的长期功能。我们证明，用I类限制性OVA特异性TCR转导的T细胞多克隆群体能够在体内持续存在，并在再次遇到同源抗原时作出反应，这可通过增殖和细胞溶解能力来评估。这些实验表明，TCR基因转移可用于产生长期的抗原特异性T细胞反应，并提供一个有用的模型系统来评估可促进经TCR修饰的T细胞高水平持久性的因素。
