Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Otolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Cancer Gene Ther. 2020 Aug;27(7-8):585-598. doi: 10.1038/s41417-019-0129-3. Epub 2019 Sep 3.
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.
治疗策略的最新进展改善了头颈部鳞状细胞癌(HNSCC)的预后。然而,5 年生存率仍仅为 40%,这需要新的治疗药物。溶瘤病毒治疗涉及使用复制能力的病毒选择性地杀死癌细胞。我们旨在探索 HF10 作为针对人类或小鼠 HNSCC 细胞系和原代培养的 HNSCC 细胞的溶瘤病毒的潜力。HF10 在所有 HNSCC 细胞中均能很好地复制,在这些细胞中,它诱导了细胞病变效应和细胞杀伤。接下来,我们研究了 HF10 在具有人或鼠肿瘤细胞的耳部肿瘤模型中的溶瘤作用。我们根据绿色荧光蛋白的表达检测到耳部肿瘤中的 HF10 感染细胞。HF10 注射抑制了耳部肿瘤的生长并延长了总生存期。在同种异体模型中,HF10 感染诱导了肿瘤坏死,并伴有 CD8 阳性细胞的浸润。此外,HF10 处理的小鼠的脾细胞在体外与肿瘤细胞刺激后释放了抗肿瘤细胞因子,IL-2、IL-12、IFN-α、IFN-β、IFN-γ和 TNF-α。在最初的肿瘤负担中幸存下来的 HF10 处理的小鼠在再次受到肿瘤细胞挑战时拒绝了肿瘤细胞。这些结果表明 HF10 杀死了 HNSCC 细胞并诱导了抗肿瘤免疫,从而确立了其作为治疗 HNSCC 患者的有前途的药物。