Evaluation of Tumor Specificity and Immunity of Thymidine Kinase-Deleted Vaccinia Virus Guang9 Strain
Evaluation of Tumor Specificity and Immunity of Thymidine Kinase-Deleted Vaccinia Virus Guang9 Strain
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胸苷激酶缺失痘苗病毒Guang9株肿瘤特异性及免疫性评价
DOI：
10.2147/ott.s260288
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Huang, Biao
中科院分区：
文献类型：
--
作者：
Ding, Yuedi;Fan, Jun;Huang, Biao
目的溶瘤病毒因其固有的肿瘤嗜性和溶瘤特性，成为临床肿瘤治疗的一种有希望的选择。除了肿瘤溶解，溶瘤病毒可以诱导宿主对肿瘤细胞的免疫应答，因此可以被视为一种免疫疗法。方法构建中国天坛株减毒痘苗病毒VG 9-Luc，表达萤火虫荧光素酶用于生物发光成像，并破坏胸苷激酶基因以增强肿瘤特异性。进行体内生物发光成像以观察病毒在活小鼠中的分布。时间分辨荧光免疫法测定血浆中抗病毒和抗肿瘤中和抗体滴度。结果除静脉注射病毒的BALB/c小鼠外，免疫功能低下和免疫功能正常的小鼠均表现出明显的肿瘤靶向性。此外，VG 9-Luc疫苗可诱导宿主产生抗病毒和抗肿瘤抗体，其过程与静脉注射和瘤内注射的病毒递送系统相似。结果表明，病毒感染通过增加抗肿瘤抗体的产生而促进肿瘤特异性免疫。此外，进行病毒再注射，与首次病毒感染相比，在免疫活性小鼠中观察到更快的病毒清除。结论胸苷激酶缺失型痘苗病毒广9株具有肿瘤特异性和抗肿瘤免疫性，是一种有希望的肿瘤治疗候选载体。
Purpose Oncolytic viruses are emerging as promising options for clinical cancer treatment due to their inherent ability of tumor tropism and oncolytic property. Aside from tumor lysis, oncolytic viruses can induce host immune responses against tumor cells and may thus be viewed as a form of immunotherapy. Methods The attenuated vaccinia VG9-Luc, which originated from Chinese vaccinia Tian Tan strain, was constructed to express firefly luciferase for bioluminescence imaging and to disrupt the thymidine kinase gene for promoting tumor specificity. An in vivo bioluminescence imaging was performed to observe the virus distribution in live mice. The titers of neutralizing antiviral and antitumor antibodies in plasma were determined by time-resolved fluoroimmunoassay. Results Except BALB/c mice treated with intravenous virus injection, all immunocompromised and immunocompetent mice showed obvious tumor targeting ability of vaccinia VG9-Luc. Besides, host immune response activated by vaccinia VG9-Luc showed the production of antiviral and antitumor antibodies, the process of which was similar between intravenous and intratumoral viral delivery systems. The results indicated that virus infection promoted tumor-specific immunity by increasing the production of antitumor antibodies. Moreover, virus reinjection was performed and a more rapid viral clearance was observed in immunocompetent mice compared with first virus infection. Conclusion The thymidine kinase-deleted vaccinia Guang9 strain, which has the properties of tumor specificity and antitumor immunity, is a promising candidate vector for cancer therapy.