CURABILITY OF TUMORS BEARING HERPES THYMIDINE KINASE GENES TRANSFERRED BY RETROVIRAL VECTORS
CURABILITY OF TUMORS BEARING HERPES THYMIDINE KINASE GENES TRANSFERRED BY RETROVIRAL VECTORS
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DOI：
10.1093/jnci/82.4.297
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发表时间：
1990-02-21
影响因子：
10.3
通讯作者：
WELLS, JM
中科院分区：
文献类型：
--
作者：
MOOLTEN, FL;WELLS, JM
构建含有单纯疱疹病毒胸苷激酶（HSV-TK）基因的逆转录病毒载体，用于将该基因转导到小鼠肉瘤和淋巴瘤细胞中，以产生体外对更昔洛韦（一种由HSV-TK特异性激活的药物）的细胞毒性敏感的亚系。在体内，更昔洛韦诱导完全的，持久的消退，在大多数小鼠移植HSV-TK阳性肉瘤;其对淋巴瘤的疗效只是边缘，可能是因为它们的基因表达更不稳定。这些结果意味着潜在的价值，需要预防性使用逆转录病毒载体的抗癌策略，以创建组织镶嵌的药物敏感性。
Retroviral vectors constructed to contain the herpes simplex virus thymidine kinase (HSV-TK) gene were used for transduction of this gene into murine sarcoma and lymphoma cells to yield sublines susceptible in vitro to the cytotoxicity of ganciclovir, a drug specifically activated by HSV-TK. In vivo, ganciclovir induced complete, durable regressions in most mice bearing transplanted HSV-TK-positive sarcomas; its efficacy against lymphomas was only marginal, possibly because of their greater instability of gene expression. The results imply the potential value of an anticancer strategy entailing the prophylactic use of retroviral vectors to create tissue mosaicism for drug sensitivity.