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构建了含ｐｇｋ启动子驱动的ＨＳＶ－ｔｋ基因的反转录病毒载体ｐＬＮＴＫ，将ＨＳＶ－ｔｋ基因转移至人脑胶质瘤ＳＨＧ４４细胞（命名为ＳＨＧＬＮＴＫ）及小鼠黑色素瘤细胞Ｂ１６（命名为Ｂ１６ＬＮＴＫ）．体外实验证实核着类似物ＡＣＶ对ＳＨＧＬＮＴＫ细胞和Ｂ１６ＬＮＴＫ细胞的杀伤敏感性分别高于亲本细胞１０００和４００倍．转ＨＳＶ－ｔｋ基因细胞与亲本细胞按不同比例共培养时，亲本细胞对ＡＣＶ的敏感性明显增高，存在旁观者效应．首次应用人脑胶质瘤细胞株进行裸鼠体内实验，结果表明：ＡＣＶ能完全抑制ＳＨＧＬＮＴＫ细胞在裸小鼠体内肿瘤的形成，对裸小鼠体内已形成的ＳＨＧＬＮＴＫ肿瘤的治疗效果与对照ＳＨＧ４４肿瘤相比，肿瘤体积缩小８０％；用Ｂ１６ＬＮＴＫ细胞接种同系Ｃ５７／ＢＬ小鼠，经ＡＣＶ治疗后，Ｂ１６ＬＮＴＫ组小鼠的肿瘤较对照组Ｂ１６肿瘤小９５％．ＨＳＶ－ＴＫ／ＡＣＶ系统原位基因转移治疗ＳＨＧ荷瘤裸小鼠、Ｂ１６荷瘤小鼠，原位注射病毒悬液／ＡＣＶ治疗组的ＳＨＧ肿瘤、Ｂ１６肿瘤分别较对照组肿瘤小５０％，４３％，原位注射ＰＡ３１７／ＬＮＴＫ细胞，ＡＣＶ治疗的ＳＨＧ肿瘤较对照组肿瘤小９０％，以上实验结果，统计学上差异极显著，Ｐ＜０．０１．实验?
The retroviral vector pLNTK containing the pgk promoter-driven HSV-tk gene was constructed, and the HSV-tk gene was transferred to human glioma SHG44 cell (named SHGLNTK) and mouse melanoma cell B16 (named B16LNTK). ). In vitro experiments confirmed that the killing susceptibility of nuclear analog ACV to SHGLNTK cells and B16LNTK cells was 1000 and 400 times higher than that of parental cells, respectively. When the HSV-tk gene transfected cells were co-cultured with parental cells in different proportions, the sensitivity of parental cells to ACV was significantly higher and there was a bystander effect. The first experiments using human glioma cell lines in nude mice showed that ACV can completely inhibit the tumor formation of SHGLNTK cells in nude mice, and the therapeutic effect of SHGLNTK tumors in nude mice was similar to that of control SHG44 tumors. In comparison, the tumor volume was reduced by 80%. After inoculation of B16LNTK cells in syngeneic C57/BL mice, the tumors in the B16LNTK group were 95% smaller than the control group B16 tumors after ACV treatment. HSV-TK/ACV system in situ gene transfer therapy in SHG tumor-bearing nude mice and B16 tumor-bearing mice. SHG tumors and B16 tumors in orally injected virus suspension/ACV treatment groups were 50% smaller than those in the control group,43 %, in situ injection of PA317/LNTK cells, ACV treatment of SHG tumors 90% smaller than the control group, the above experimental results, the statistically significant difference, P <0.01. experiment?