Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild type tumor.
Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild type tumor.
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表达胞嘧啶脱氨酶自杀基因的肿瘤可以在体内用5-氟胞嘧啶消除，并诱导针对野生型肿瘤的保护性免疫。
作者：
C. Mullen;M. Coale;R. Lowe;R. Blaese
胞嘧啶脱氨酶（CD）自杀基因在体内的成功表达证明在三个弱免疫原性小鼠肿瘤模型：102和205纤维肉瘤和38腺癌。正常哺乳动物细胞不含胞嘧啶脱氨酶，但用含有CD基因的逆转录病毒载体转导的肿瘤细胞将相对无毒的前药5-氟胞嘧啶代谢为高毒性的5-氟尿嘧啶。在体外表达CD基因的细胞被5-氟胞嘧啶杀死，而未修饰的细胞不会。当注射到同系小鼠中时，CD+肿瘤也可以通过用5-氟胞嘧啶全身治疗在体内消除，而对宿主没有显著毒性。用前药治疗消除CD+肿瘤的动物抵抗随后用未修饰的野生型肿瘤的再攻击。这种治疗后免疫似乎是肿瘤特异性的。讨论了CD系统在基因治疗模型中的应用。
Successful expression of the cytosine deaminase (CD) suicide gene in vivo is demonstrated in three weakly immunogenic murine tumor models: the 102 and 205 fibrosarcomas and the 38 adenocarcinoma. Normal mammalian cells do not contain cytosine deaminase, but tumor cells transduced with retroviral vectors containing the CD gene metabolize the relatively nontoxic prodrug 5-fluorocytosine to the highly toxic 5-fluorouracil. In vitro cells expressing the CD gene are killed by 5-fluorocytosine while unmodified cells are not. When injected into syngeneic mice, CD+ tumors can also be eliminated in vivo by systemic treatment with 5-fluorocytosine without significant toxicity to the host. Animals whose CD+ tumors were eliminated with prodrug treatment resist subsequent rechallenge with unmodified wild type tumor. This posttreatment immunity appears to be tumor specific. Applications of the CD system in gene therapy models are discussed.
DOI：
10.1073/pnas.88.4.1330
发表时间：
1991-02-01
影响因子：
11.1
作者：
PALMER, TD;ROSMAN, GJ;MILLER, AD
通讯作者：
MILLER, AD