Luo Yong, Lin Chaolong, Zou Yidi, Ju Fei, Ren Wenfeng, Lin Yanhua, Wang Yale, Huang Xiaoxuan, Liu Huiling, Yu Zeng, Liu Pingguo, Tan Guowei, Yuan Quan, Zhang Jun, Huang Chenghao, Xia Ningshao
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen, Fujian, China.
Department of Hepatobiliary Surgery, Zhongshan Hospital Xiamen University, Xiamen, Fujian, China.
Oncoimmunology. 2020 Feb 12;9(1):1726168. doi: 10.1080/2162402X.2020.1726168. eCollection 2020.
Oncolytic viruses represent a promising therapeutic modality, but they have yet to live up to their therapeutic potential. Safety and efficacy concerns impel us to identify least toxic oncolytic agents that would generate durable and multifaceted anti-tumor immune responses to disrupt the tumors. Here we describe a rational engineered oncolytic herpes virus (OVH) that is a selective killer for targeting tumors, has strong safety records, induces complete regression of tumors in multiple tumor models, and elicits potent antitumor immunity. By far, the potential of OVs in promoting the tumor antigen-specific humoral immune responses remains obscure. In this study, we found that effective treatment by OVH induced immunogenic cell death, which facilitates to elicit humoral immune responses. Depletion experiments revealed that B cells were required for maximal antitumor efficacy of oncolytic immunotherapy. Both serum transfer and antibody treatment experiments revealed that endogenous oncolysis-induced antigen-targeting therapeutic antibodies can lead to systemic tumor regression. Our data demonstrate that tumor-targeting immune modulatory properties confer oncolytic OVH virotherapy as potent immunotherapeutic cancer vaccines that can generate specific and efficacious antitumor humoral responses by eliciting endogenous tumor antigen-targeting therapeutic antibodies , resulting in an efficacious and tumor-specific therapeutic effect.
溶瘤病毒是一种很有前景的治疗方式，但它们尚未充分发挥其治疗潜力。对安全性和有效性的担忧促使我们去寻找毒性最小的溶瘤药物，这些药物能够产生持久且多方面的抗肿瘤免疫反应以破坏肿瘤。在此，我们描述了一种经过合理设计的溶瘤疱疹病毒（OVH），它是一种靶向肿瘤的选择性杀手，具有良好的安全记录，能在多种肿瘤模型中使肿瘤完全消退，并引发强大的抗肿瘤免疫力。到目前为止，溶瘤病毒在促进肿瘤抗原特异性体液免疫反应方面的潜力仍不明确。在本研究中，我们发现OVH的有效治疗诱导了免疫原性细胞死亡，这有助于引发体液免疫反应。耗竭实验表明，B细胞是溶瘤免疫疗法实现最大抗肿瘤疗效所必需的。血清转移和抗体治疗实验均表明内源性溶瘤诱导的靶向抗原治疗性抗体可导致全身性肿瘤消退。我们的数据表明，靶向肿瘤的免疫调节特性赋予溶瘤OVH病毒疗法作为有效的免疫治疗性癌症疫苗的能力，该疫苗可通过引发内源性靶向肿瘤抗原的治疗性抗体产生特异性且有效的抗肿瘤体液反应，从而产生有效的肿瘤特异性治疗效果。
