逆转录病毒载体介导的CD基因对小鼠胃癌的原位杀伤作用

目的　探讨自杀基因的旁观者效应及引发的抗肿瘤免疫对胃癌的治疗作用。方法　将含有ＣＤ基因的重组逆转录病毒载体ｐＣＤ２ 在ＰＡ３１７ 细胞中进行包装后，收获病毒上清；将此上清直接注射接种于６１５ 小鼠皮下并已成瘤的ＭＦＣ小鼠前胃癌的肿瘤部位，再腹腔给予前药５ＦＣ 进行治疗。治疗结束后，检测ＮＫ、ＬＡＫ细胞活性以判断机体免疫活性。结果　在前药治疗阶段中，转ＣＤ基因肿瘤较未转基因肿瘤的生长明显受抑，且有部分肿瘤消失（ Ｐ＜０ ．０１ ，ｎ＝１０） 。在成瘤对照组中，ＮＫ、ＬＡＫ 活性受到抑制，低于正常对照组，而ＣＤ／５ＦＣ组的ＮＫ、ＬＡＫ活性明显增高。肿瘤消失小鼠在远离原肿瘤部位再接种ＭＦＣ细胞，９０ 天后均未见肿瘤生长且长期存活。结论　在胃癌肿瘤部位直接转导ＣＤ 基因不仅可以对肿瘤产生强效的杀伤作用，由此引发的抗肿瘤免疫反应对阻止肿瘤复发有重要意义。

Insitu anti tumor effect for stomach neoplasm implanted on 615 mice resulting from cytosine deaminase gene deliveried by retrovirial vector

Objective To seek an effecfive way to kill gastric cancer cells directly involving bystander effect and succesive anti tumor effect resulting from cytosine deaminase gene mediated by retroviral vector.Method The murine gastric cancer line MFC were injected s.c.into the flank of 615 mice. When tumors were palpable, 0.2ml retroviral supernatant containing pCD2 gene was directly transduced into tumors following administration of 5 FC for 3 weeks. At the end of treatment, mice were sacrifice and pathologic eximination was taken, and NK, LAK activity of murine were examined.Results Profound antitumor effect was observed in tumors generated from MFC CD( ) tumors when the animals were given 5 FC by i.p. The tumors generated from MFC cells had a histological pattern similar to that of untreated animals with few areas of detectable necrosis. In cotrast, the tumors under the treatment of 5 FC/CD had a large scale necrosis resions compared with that of untreated animals. It was noteworthy that a second attempt in tumor transplanttation of MFC cells were failed in any of the mice with tumor completely regression.Conclusion The improvement of the anti tumor effect by directly transduction of CD gene in tumors rends a basis of further reserch to gastric carcinoma, and the anti tumor immune effect resulting from suicide gene support the continued development of a clinical gene therapy to prevent reccurence of gastric carcinoma.;