Oncolytic Sendai virus for brain-tsupmeorcific immune-gene therapy

胶质母细胞瘤（GM）是高度侵袭性的，由于蛋白酶的表达，包括尿激酶型纤溶酶原激活物（uPA）。一种新的具有upa特异性细胞间融合活性的重组仙台病毒（rSeV） [rSeV/dMFct14 (uPA2)]被证明对转基因治疗有效，特别是与干扰素-β (IFN-β)基因整合。脑肿瘤组织中CD8 T细胞、CD4 T细胞、CD11b+细胞明显浸润。在rSeV/dMFct14 (uPA2)/ IFNβ治疗的肿瘤组织中，Flt3-L也高度阳性，这被认为是突出的免疫原性的分子背景。在长期存活的大鼠中未观察到不良事件。因此，这些结果表明，在临床环境中，rSeV/dMFct14 (uPA2)/ IFNβ可能具有显著的改善GM患者生存的潜力。

Glioblastoma (GM) is highly invasive due to the expression of proteases including urokinase-type plasminogen activator (uPA). A new recombinant Sendai virus (rSeV) showing uPA-specific cell-to-cell fusion activity [rSeV/dMFct14 (uPA2)] was shown to be effective for GM treatment, especially with the interferon-β (IFN-β) gene integration. There were marked infiltration of CD8 T cell, CD4 T cell, and CD11b+ cells in the brain tumor tissues. Flt3-L was also highly positive in the tumor tissues treated with rSeV/dMFct14 (uPA2)/ IFNβ, which was considered to be the molecular background of the prominent immunogeneicity. There were no adverse events observed in the long-survived rats. Therefore, these results suggest that rSeV/dMFct14 (uPA2)/ IFNβ may have a significant potential to improve the survival of GM patients in a clinical setting.