摘要
目的 探讨逆转录病毒载体介导的白细胞介素 (IL) 4和γ 干扰素 (IFN )基因联合治疗胶质瘤的作用。方法 构建携带IL 4或IFN γ基因的逆转录病毒载体 ,将其导入逆转录病毒包装细胞 ;将携带IL 4和IFN γ基因的逆转录病毒包装细胞分别或联合注射到脑内荷瘤大鼠的肿瘤组织中 ,观察其治疗作用。结果 成功获得携带治疗基因的逆转录病毒包装细胞PA3 17IFN γ和PA3 17IL 4,所产病毒滴度分别为 2× 10 6cfu/ml和 2 .5× 10 6cfu/ml。包装细胞瘤内注射能够诱导大鼠产生抗肿瘤免疫反应 ,杀伤肿瘤细胞 ,联合应用具有协同治疗作用。结论 携带IL 4或IFN γ基因的逆转录病毒包装细胞瘤内注射是一种有效的胶质瘤基因治疗方法 ,两者联合应用具有协同治疗作用。
Objective To investigate the therapeutic effects of retrovirus vector mediated genes transfer of γ interferon (IFN γ) and interleukin 4 (IL 4) in the treatment of C6 glioma.Methods Retrovirus vectors encoding IFN γ or IL 4 gene were transfected into PA317 packaging cells.The intracranial C6 glioma animal model was established in immunocompetent Wistar rats.PA317IFN γ and PA317IL 4 cells were stereotactically implanted into the tumor areas alone or together.The survival of tumor bearing rats was examined,tumor volumes measured and immunohistochemical analyses of CD4 + and CD8 + T lymphocyte infiltration performed.Results Tumor growth was suppressed and the rats bearing glioma survived longer by in situ implanted PA317IFN γ or PA317IL 4 cells.Immunohistochemical analyses revealed that tumor growth arrest was associated with an infiltration of greater number CD4 + and CD8 + T lymphocyte in tumor areas.The therapeutic effects of PA317IFN γ and PA317IL 4 together were better than themselves alone.Conclusion Implantation of retroviral packaging cells containing IL 4 and IFN γ genes into established intracranial gliomas lead to tumor growth arrest that was associated with an infiltration of greater number CD4 + and CD8 + T lymphocyte in tumor areas.The therapeutic effects of PA317IFN γ and PA317IL 4 together were better than themselves alone.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2004年第6期733-734,i006,共3页
Chinese Journal of Experimental Surgery