Improving the safety of cell therapy products by suicide gene transfer.
Improving the safety of cell therapy products by suicide gene transfer.
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DOI：
10.3389/fphar.2014.00254
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发表时间：
2014
影响因子：
5.6
通讯作者：
Di Stasi A
中科院分区：
文献类型：
--
作者：
Jones BS;Lamb LS;Goldman F;Di Stasi A
连续性T细胞疗法可涉及同种异体造血干细胞移植后的供体淋巴细胞输注，离体扩增的肿瘤浸润淋巴细胞的施用，或最近使用T细胞受体或嵌合抗原受体重定向的T细胞。然而，细胞疗法可能会带来重大风险，包括移植物抗肿瘤。宿主疾病和其他靶上和靶外效应，因此需要实施战略，永久扭转任何毒性迹象。自杀基因是一种遗传编码的分子，它允许选择性破坏过继转移的细胞。向细胞治疗产品中添加自杀基因可以导致基因修饰细胞的选择性消融，防止对邻近细胞和/或组织的附带损伤。“理想的”自杀基因将通过不可逆地消除“所有”且“仅”导致有害毒性的细胞来确保基因修饰细胞应用的安全性。本文综述了迄今为止报道的自杀基因安全系统，重点是关于两个最广泛验证的自杀基因的最新技术和潜在应用，包括临床背景：单纯疱疹病毒胸苷激酶和诱导型caspase-9。
Adoptive T-cell therapy can involve donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation, the administration of tumor infiltrating lymphocyte expanded ex-vivo, or more recently the use of T cell receptor or chimeric antigen receptor redirected T cells. However, cellular therapies can pose significant risks, including graft-vs.-host-disease and other on and off-target effects, and therefore strategies need to be implemented to permanently reverse any sign of toxicity. A suicide gene is a genetically encoded molecule that allows selective destruction of adoptively transferred cells. Suicide gene addition to cellular therapeutic products can lead to selective ablation of gene-modified cells, preventing collateral damage to contiguous cells and/or tissues. The “ideal” suicide gene would ensure the safety of gene modified cellular applications by granting irreversible elimination of “all” and “only” the cells responsible for the unwanted toxicity. This review presents the suicide gene safety systems reported to date, with a focus on the state-of-the-art and potential applications regarding two of the most extensively validated suicide genes, including the clinical setting: herpes-simplex-thymidine-kinase and inducible-caspase-9.