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目的:探讨人类复制缺陷型重组腺病毒载体介导mIFN-β基因治疗小鼠黑色素瘤的可行性和效果。方法:利用人类复制缺陷型重组腺病毒将目的基因mIFN-β经体外、体内两种途径导入小鼠黑色素瘤细胞(B16细胞)中,观察体外转mIFN-β基因的B16细胞的体内致瘤性和瘤苗作用,及通过腺病毒载体介导的mIFN-β对体内局部肿瘤治疗和抗肿瘤转移的作用。结果:1)携带目的基因的重组腺病毒感染B16细胞能获得较高的转移效率和目的基因的有效表达;2)将mIFN-β基因导入B16细胞对B16细胞的体外增殖能力无明显影响,但能显著提高细胞表面MHC-I类抗原的表达;3)将转mIFN-β基因的B16细胞接种小鼠,其体内致瘤性明显降低,且对对侧野生型B16细胞的致瘤性有抑制作用;4)瘤体内注射和经尾静脉注射途径给予AdCMVmIFN-β,对局部肿瘤和转移瘤有治疗作用。结论:利用人类复制缺陷型腺病毒载体介导mIFN-β基因治疗小鼠黑色素瘤是可行的,并具有较好疗效,提示用腺病毒载体携带有效的目的基因来开发瘤苗和治疗肿瘤具有良好的临床应用前景。
Objective: To investigate the feasibility and efficacy of human replication-defective recombinant adenoviral vector-mediated mIFN-β gene therapy in mouse melanoma. METHODS: Human mIFN-β gene was introduced into mouse melanoma cells (B16 cells) by human replication-defective recombinant adenoviruses in vitro and in vivo, and in vivo tumorigenicity of B16 cells transfected with mIFN-β gene was observed. Roles with tumor vaccines and by adenoviral vectors mediated the effect of mIFN-β on local tumor treatment and antitumor metastasis in vivo. RESULTS: 1) The recombinant adenovirus carrying the target gene infects B16 cells can obtain high transfer efficiency and effective expression of the target gene; 2) The introduction of mIFN-β into B16 cells has no significant effect on the proliferation of B16 cells in vitro, but It can significantly increase the expression of MHC class I antigens on the cell surface; 3) The mice inoculated with B16 cells transfected with mIFN-β gene have significantly reduced tumorigenicity in vivo and inhibit tumorigenicity of the wild type B16 cells on the opposite side. The role of; 4) intratumoral injection and via tail vein injection of AdCMVmIFN-β, a treatment of local tumors and metastases. Conclusion: The use of human replication-defective adenoviral vector-mediated mIFN-β gene therapy in mouse melanoma is feasible and has good curative effect, suggesting that using adenovirus vector to carry effective target gene to develop tumor vaccine and treat tumor has good The clinical application prospects.