将人CD20作为自杀基因进行逆转录病毒转导用于过继性T细胞治疗。
Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy.
作者信息
Griffioen Marieke, van Egmond Esther H M, Kester Michel G D, Willemze Roel, Falkenburg J H Frederik, Heemskerk Mirjam H M
机构信息
Department of Hematology, Laboratory of Experimental Hematology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.
出版信息
Haematologica. 2009 Sep;94(9):1316-20. doi: 10.3324/haematol.2008.001677.
The aim of adoptive T-cell therapy of cancer is to selectively confer immunity against tumor cells. Autoimmune side effects, however, remain a risk, emphasizing the relevance of a suicide mechanism allowing in vivo elimination of infused T cells. We investigated the use of human CD20 as suicide gene in T-lymphocytes. Potential effects of forced CD20 expression on T-cell function were investigated by comparing CD20- and mock-transduced cytomegalovirus (CMV) specific T cells for cytolysis, cytokine release and proliferation. The use of CD20 as suicide gene was investigated in CMV specific T cells and in T cells genetically modified with an antigen specific T-cell receptor. No effect of CD20 on T-cell function was observed. CD20-transduced T cells with and without co-transferred T-cell receptor were efficiently eliminated by complement dependent cytotoxicity induced by therapeutic anti-CD20 antibody rituximab. The data support the broad value of CD20 as safety switch in adoptive T-cell therapy.
癌症过继性T细胞疗法的目的是选择性地赋予针对肿瘤细胞的免疫力。然而，自身免疫副作用仍然是一种风险，这凸显了一种自杀机制的重要性，该机制可在体内清除注入的T细胞。我们研究了将人CD20用作T淋巴细胞中的自杀基因。通过比较CD20转导和模拟转导的巨细胞病毒（CMV）特异性T细胞的细胞溶解、细胞因子释放和增殖情况，研究了强制表达CD20对T细胞功能的潜在影响。在CMV特异性T细胞和用抗原特异性T细胞受体进行基因改造的T细胞中研究了将CD20用作自杀基因的情况。未观察到CD20对T细胞功能有影响。携带和不携带共转移T细胞受体的CD20转导T细胞可被治疗性抗CD20抗体利妥昔单抗诱导的补体依赖性细胞毒性有效清除。这些数据支持了CD20作为过继性T细胞疗法安全开关的广泛价值。
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