瘤体注射IL-2重组腺病毒基因治疗小鼠胶质母细胞瘤及其免疫机制的初步探讨

目的：观察瘤体直接注射IL－2重组腺病毒对G422皮下荷瘤的治疗作用，对体内基因转染效率及治疗的免疫机制进行初步分析。方法：将LacZ,IL-2重组腺病毒直接注射到皮下接种的G422胶质母细胞瘤瘤体，X－gal染色检测基因转染的效率，观察肿瘤的大小和荷瘤小鼠的存活期，采用4h^51Cr释放法检测荷瘤小鼠脾细胞诱导的NK、LAK、CTL的杀伤活性，对治疗后的肿瘤进行常规病理分析。结果：采用瘤体注射腺病毒具有较高的体内基因转染效率，瘤体注射IL－2重组腺病毒对皮下建立的胶质母细胞瘤有一定的治疗作用，肿瘤的生长受抑制，荷瘤小鼠的存活期显延长，但没有长期存活小鼠。IL－2基因治疗组小鼠脾细胞的LAK、CTL杀伤活性显增强，肿瘤局部出现更多的坏死和炎性浸润细胞。结论：采用瘤体直接注射IL－2重组腺病毒对胶质母细胞瘤皮下荷瘤有治疗,其机制可能是增强了宿主的局部和全身抗肿瘤免疫反应。

Therapeutic effects and immunological mechanism of IL-2 gene therapy for glioblastoma by intratumoral injection of IL-2 recombinant adenovirus

Objective: : To evaluate the efficiency of gene tr an sfection in vivo , and to study the therapeutic effects and immunological me chanism of IL 2 gene therapy for G422 glioblastoma by intratumoral injection of IL 2 recombinant adenovirus. Methods: Recombinant adenoviruses e ncoding Lac Z, IL 2 gene were directly injected into G422 glioblastomas establ ished subcutaneously. X gal staining was used to evaluate the efficiency of gen e transfection. The tumor size and survival time of tumor bearing mice were obse rved. The splenic NK, LAK, and CTL cytotoxicities were analyzed by standard 4 h 51 Cr release assay. The histological characteristics after gene thera py were also observed. Results: Direct intratumoral injection of rec ombinant adenovirus achieved relatively high rate of gene transfection. IL 2 ge ne therapy had therapeutic effects on subcutaneous G422 glioblastomas model. The tumor bearing mice showed significant prolongation of survival time, significan t enhancement of splenic LAK and CTL cytotoxicities. Histological examination sh owed much more necrosis and inflammatory cell infiltration in the tumors of the IL 2 gene therapy group. Conclusion: Intratumoral injection of IL 2 recombinant adenovirus has potent therapeutic effects on subcutaneously establ ished G422 glioblastomas, and the mechanisms involved may be related to enhancem ent of regional and systemic anti tumor immune response.