复制缺陷型重组腺病毒介导mIFN-β基因治疗小鼠黑色素瘤的研究  

The Studies on Gene Therapy for Murine Melanoma by Replication-defective Recombinant Adenovirus-Induced mIFN-β gene

作　　者：张明霞[1] 吴云[1] 邓松华[1] 卢海妹[1] 蔡春晓[1] 徐容[1] 曹广文[2] 潘卫[2] 陈秋莉[2] 沈毅君 

机构地区：[1]安徽医科大学病理生理教研室,合肥市230032 [2]第二军医大学微生物教研室 [3]复旦张江生物医药股份公司

出　　处：《中国肿瘤临床》2006年第1期20-24,共5页Chinese Journal of Clinical Oncology

基　　金：安徽省教育厅自然科学基金资助（编号：2001kj143）

摘　　要：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 study the feasibility and effect of gene therapy for murine melanoma by replication-defective recombinant adenovirus-induced mlFN-β gene. Methods： The gene of murine interferon beta （mlFN-β） was transduced into routine melanoma cells B16 by human replicationdefective recombinant adenovirus via ex vivo and in vivo respectively, then the tumorigenicity, tumor vaccine effect and anti-tumor effect were investigated. Results： 1） The recombinant adenoviruses harboring foreign gene infecting B16 cells had high efficiency of gene transfer and expression; 2） The transfection of AdmlFN-β had no effect on the growth rate of B16 cells, but the expression of major histocompatibility complex class （MHC-I） of those cells was obviously enhanced; 3） In mouse experiments, ex vivo mlFN-β gene delivered into B16 cells by adenovirus not only resulted in an efficient inhibition of tumorigenicity in situ, but also led to a growth inhibition of parental cells at other sites; 4） Giving AdCMVmlFN-β through i.t. and i.v resulted in a significant anti-tumor effect on subcutaneous tumors and lung metastasis. Conclusion： It＇s feasible and effective of gene therapy for murine melanoma by replication-defective recombinant adenovirus harboring mlFN-β gene. This study indicates it has bright prospect to develop tumor vaccine and treat tumor by using adenovirus vector harboring a certain gene.

关 键 词：重组腺病毒 Β-干扰素 黑色素瘤 基因治疗 

分 类 号：R73-36[医药卫生—肿瘤]