HF10在头颈部鳞状细胞癌中的溶瘤活性
Oncolytic activity of HF10 in head and neck squamous cell carcinomas
原文发布日期:2019-09-03
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Recent developments in therapeutic strategies have improved the prognosis of head and neck squamous cell carcinoma (HNSCC). Nevertheless, 5-year survival rate remains only 40%, necessitating new therapeutic agents. Oncolytic virotherapy entails use of replication-competent viruses to selectively kill cancer cells. We aimed to explore the potential of HF10 as an oncolytic virus against human or mouse HNSCC cell lines, and primary-cultured HNSCC cells. HF10 replicated well in all the HNSCC cells, in which it induced cytopathic effects and cell killing. Next, we investigated the oncolytic effects of HF10 in ear tumor models with human or mouse tumor cells. We detected HF10-infected cells within the ear tumors based on their expression of green fluorescent protein. HF10 injection suppressed ear tumor growth and prolonged overall survival. In the syngeneic model, HF10 infection induced tumor necrosis with infiltration of CD8-positive cells. Moreover, the splenocytes of HF10-treated mice released antitumor cytokines, IL-2, IL-12, IFN-alpha, IFN-beta, IFN-gamma, and TNF-alpha, after stimulation with tumor cells in vitro. The HF10-treated mice that survived their original tumor burdens rejected tumor cells upon re-challenge. These results suggested that HF10 killed HNSCC cells and induced antitumoral immunity, thereby establishing it as a promising agent for the treatment of HNSCC patients.
近年来,治疗策略的新进展改善了头颈鳞状细胞癌(HNSCC)的预后,但患者五年生存率仍仅为40%,亟需开发新型治疗药物。溶瘤病毒疗法利用具有复制能力的病毒选择性杀伤癌细胞。本研究旨在探讨HF10作为溶瘤病毒对人源及鼠源HNSCC细胞系、以及原代培养HNSCC细胞的抗肿瘤潜力。HF10在所有HNSCC细胞中均表现出良好复制能力,并诱导细胞病变效应和细胞杀伤。随后,我们在人源和鼠源肿瘤细胞的耳部肿瘤模型中评估HF10的溶瘤效果:通过绿色荧光蛋白表达确认病毒成功感染耳部肿瘤细胞;HF10注射显著抑制耳部肿瘤生长并延长总生存期。在同系移植瘤模型中,HF10感染诱导肿瘤坏死并伴随CD8阳性细胞浸润。更重要的是,经HF10处理的小鼠脾细胞在体外经肿瘤细胞刺激后,可释放抗肿瘤细胞因子IL-2、IL-12、IFN-α、IFN-β、IFN-γ和TNF-α。存活小鼠在二次接种肿瘤细胞时表现出完全排斥反应。这些结果表明,HF10不仅能有效杀伤HNSCC细胞,还能诱导抗肿瘤免疫应答,因此有望成为治疗HNSCC患者的有效制剂。
Oncolytic activity of HF10 in head and neck squamous cell carcinomas
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