共表达BiTE的溶瘤病毒对胶质瘤的抗肿瘤活性研究

目的:探索编码BiTE的溶瘤病毒分泌双特异性T细胞衔接器的单纯性孢疹病毒(herpes simplex virus-Bi-specific T-cell engagers,HSV-BiTE)]是否可以对胶质瘤产生显著的抗肿瘤活性.方法:荧光显微镜观察及Western blot检测HSV-BiTE对胶质瘤细胞U118的...

Antitumor activity of oncolytic virus co-expressing BiTE against glioma

Objective:To explore whether oncolytic virus encoding BiTE (herpes simplex virus-Bi-specific T-cell engagers，HSV-BiTE) can produce significant anti-tumor activity against glioma.Methods:The infection ability of HSV-BiTE to glioma cell line U118 and the expression of BiTE were detected by fluorescence microscope and Western blot.The apoptosis of U118 after HSV-BiTE infection was detected by flow cytometry.The in vivo antitumor activity of HSV-BiTE was verified by mouse tumor transplantation model.The expression of Ki67 and Cleaved Caspase3 (Cl-Cas3) in tumor tissue were detected by immunohistochemistry.The expression of IFN-γ and Granzyme B in tumor infiltrating T cells was detected by flow cytometry.Results:HSV-BiTE can effectively infect U118 cells and express BiTE.HSV-BiTE can significantly induce U118 cell apoptosis （P＜0.001）.HSV-BiTE can effectively inhibit tumor growth in mice compared with HSV （P＜0.001）.Compared with HSV,HSV-BiTE-treated mice could reduce the expression of Ki67 （P＜0.01） and increase the expression of Cl-Cas3 （P＜0.01） in tumor,while HSV-BiTE-treated mice could significantly increase the expression of IFN-γ （P＜0.001） and Granzyme B （P＜0.000 1） in tumor infiltrating T cells than HSV.Conclusion:HSV-BiTE can significantly inhibit tumor growth and stimulate tumor infiltrating T cells to exert anti-tumor function in subcutaneously transplanted tumor model in mice.This treatment is superior to unmodified HSV therapy and supports further study of its application in glioma.