GM-CSF基因修饰的肿瘤细胞疫苗对荷瘤小鼠的抗肿瘤作用

Antitumor effect of GM-CSF gene modified murine EL-4 cell vaccine

目的 :研究GM CSF基因修饰的肿瘤细胞作为瘤苗的可行性。方法 :通过逆转录病毒载体 ,将小鼠GM CSF基因导入EL 4淋巴瘤细胞中 ,研究EL 4 GM CSF在同系C5 7BL 6小鼠中的成瘤性及其诱导抗肿瘤免疫的效果。结果 :EL 4 GM CSF细胞在小鼠中的成瘤性下降 ,5 0 %小鼠无瘤生存。射线灭活的EL 4 GM CSF瘤苗能有效地保护野生型肿瘤细胞的攻击 ,在肿瘤生长的早期对实验性荷瘤小鼠进行治疗 ,能延长荷瘤宿主的存活时间(33 1± 1 8)与对照组EL 4 Wt(2 3 2± 1 5天 )比差异有显著性 (P <0 0 1)。基因修饰的瘤苗作用明显增强。结论 :GM CSF基因修饰的肿瘤疫苗可诱导较强的抗肿瘤免疫反应 ,导致肿瘤的部分根除 ,本实验为基因修饰的肿瘤疫苗的临床应用提出了一定的实验依据。

Purpose:To study the vaccine potency of gene-modified tumor cells.Methods:The EL-4 lymphoma was transduced with recombinant retrovirus containing the murine GM-CSF gene. The effect of gene transduction on antitumor immunity was investigated.Results:There was no significant difference in the morphology, growth rate and expression of their surface marker between EL-4 cells and gene transduced EL-4 cells. GM-CSF gene transduced EL-4 cells resulted in remarkable loss of tumorigenicity in syngenetic mice. EL-4/GM-CSF cells could induce strong protective immune reaction. Therapeutic vaccine of EL-4/GM-CSF cells could significantly retard the growth of established early-stage EL-4/wt tumor, but did not retard the growth of late-stage EL-4/wt tumor. Irradiated GM-CSF gene transduced EL-4 cells showed strong vaccine effect against challenged EL-4 cells. Conclusions:GM-CSF gene transduced EL-4 cells can be called a good tumor vaccine. It suggested that this vaccine has potential application value in human cancer treatment.