Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, People's Republic of China.
Department of Obstetrics and Gynecology, Zhongshan Hospital, Xiamen University, Xiamen, 361004, People's Republic of China.
Virol J. 2018 Apr 10;15(1):65. doi: 10.1186/s12985-018-0975-x.
Endometrial cancer (EC) is one of the most common gynecological malignancies globally. Although progress has been made in surgical and other adjuvant therapies, there is still a great need to develop new approaches to further reduce the incidence and mortality of EC. Oncolytic virotherapy offers a novel promising option of cancer treatment and has demonstrated good efficacy in preclinical models and clinical trials. However, only few oncolytic viruses have been tested for EC treatment. In this study, the potential of an oncolytic coxsackievirus B3 (CV-B3) strain 2035A (CV-B3/2035A) was investigated as a novel biotherapeutic agent against EC.
Human EC cell lines (Ishikawa, HEC-1-A and HEC-1-B) were infected with CV-B3/2035A, and viral replication and cytotoxic effects were evaluated in vitro. CV-B3/2035A-induced oncolysis was also investigated in nude mice bearing EC xenografts in vivo and in patient-derived EC samples ex vivo.
Human EC cell lines expressing different levels of CAR and DAF were all susceptible to infection by CV-B3/2035A and supported efficient viral replication in vitro. In the EC xenograft/nude mouse model, both intratumoral and intravenous administrations of CV-B3-2035A exerted significant therapeutic effects against pre-established EC tumors without causing significant treatment-related toxicity and mortality in nude mice. Moreover, CV-B3/2035A treatment resulted in decreased viability of patient-derived EC samples ex vivo.
CV-B3/2035A showed oncolytic activity in human EC cell lines both in vitro and in vivo as well as in patient-derived EC samples ex vivo and thus could be used as an alternative virotherapy agent for the treatment of EC.
子宫内膜癌（EC）是全球最常见的妇科恶性肿瘤之一。尽管在手术和其他辅助治疗方面取得了进展，但仍迫切需要开发新方法来进一步降低 EC 的发病率和死亡率。溶瘤病毒治疗为癌症治疗提供了一种新的有前途的选择，并在临床前模型和临床试验中显示出良好的疗效。然而，只有少数溶瘤病毒被用于治疗 EC。在这项研究中，研究人员探索了一种溶瘤柯萨奇病毒 B3（CV-B3）株 2035A（CV-B3/2035A）作为治疗 EC 的新型生物治疗剂的潜力。
用人子宫内膜癌细胞系（Ishikawa、HEC-1-A 和 HEC-1-B）感染 CV-B3/2035A，在体外评估病毒复制和细胞毒性作用。还在携带 EC 异种移植瘤的裸鼠体内和患者来源的 EC 样本体外研究了 CV-B3/2035A 诱导的溶瘤作用。
表达不同水平 CAR 和 DAF 的人 EC 细胞系均易受 CV-B3/2035A 感染，并在体外支持有效的病毒复制。在 EC 异种移植瘤/裸鼠模型中，CV-B3-2035A 的肿瘤内和静脉内给药均对已建立的 EC 肿瘤产生了显著的治疗效果，而在裸鼠中没有引起明显的治疗相关毒性和死亡率。此外，CV-B3/2035A 处理导致患者来源的 EC 样本体外的活力降低。
CV-B3/2035A 在人子宫内膜癌细胞系中无论是在体外还是体内以及患者来源的 EC 样本中均显示出溶瘤活性，因此可作为治疗 EC 的替代病毒治疗剂。
