Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy
Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy
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DOI：
10.1182/blood.v99.6.2009
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发表时间：
2002-03-15
期刊：
影响因子：
20.3
通讯作者：
Brenner, MK
中科院分区：
文献类型：
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作者：
Rossig, C;Bollard, CM;Brenner, MK
表达肿瘤或病毒抗原特异性嵌合受体的原代T细胞具有相当大的治疗潜力。不幸的是，它们的临床价值受到限制，因为它们的功能迅速丧失，无法在体内扩展，这可能是由于肿瘤细胞上缺乏共刺激分子，以及仅通过嵌合受体传递信号的固有局限性。eb病毒（EBV）感染B淋巴细胞在人类中几乎是普遍存在的，它会刺激高水平的EBV特异性辅助细胞和细胞毒性T细胞，这些细胞会无限期地持续存在。我们的临床研究表明，体外产生的ebv特异性T细胞在体内可以扩增、持续存在并发挥作用超过6年。我们现在报道ebv特异性（但不是原代）T细胞通过肿瘤特异性嵌合受体基因转导，可以在ebv感染的B细胞存在下扩增并长期维持。它们通过传统的t细胞受体识别ebv感染的靶标，通过嵌合受体识别肿瘤靶标。它们能有效地溶解这两种物质。表达嵌合抗肿瘤受体的ebv特异性T细胞可能代表了一种新的效应细胞来源，这种效应细胞在转移到癌症患者体内后将持续存在并长期发挥作用。
Primary T cells expressing chimeric receptors specific for tumor or viral antigens have considerable therapeutic potential. Unfortunately, their clinical value is limited by their rapid loss of function and failure to expand in vivo, presumably due to the lack of costimulator molecules on tumor cells and the inherent limitations of signaling exclusively through the chimeric receptor. Epstein-Barr virus (EBV) infection of B lymphocytes is near universal in humans and stimulates high levels of EBV-specific helper and cytotoxic T cells, which persist indefinitely. Our clinical studies have shown that EBV-specific T cells generated in vitro will expand, persist, and function for more than 6 years in vivo. We now report that EBV-specific (but not primary) T cells transduced with tumor-specific chimeric receptor genes can be expanded and maintained long-term in the presence of EBV-infected B cells. They recognize EBV-infected targets through their conventional T-cell receptor and tumor targets through their chimeric receptors. They efficiently lyse both. EBV-specific T cells expressing chimeric antitumor receptors may represent a new source of effector cells that would persist and function long-term after their transfer to cancer patients.