Moolten F L, Wells J M
Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA 01730.
J Natl Cancer Inst. 1990 Feb 21;82(4):297-300. doi: 10.1093/jnci/82.4.297.
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.
构建的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鼠肉瘤和淋巴瘤细胞中，以产生在体外对更昔洛韦（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，更昔洛韦使大多数携带移植的HSV-TK阳性肉瘤的小鼠产生完全、持久的肿瘤消退；其对淋巴瘤的疗效仅为边缘性，可能是因为它们基因表达的稳定性较差。这些结果表明了一种抗癌策略的潜在价值，该策略需要预防性使用逆转录病毒载体来产生对药物敏感的组织镶嵌现象。
