Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic metastases.
Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic metastases.
复制标题
DOI：
10.1089/104303402320138998
复制
发表时间：
2002-07
影响因子：
4.2
通讯作者：
R. Wong;J. Joe;Se-Heon Kim;J. Shah;B. Horsburgh;Y. Fong
中科院分区：
文献类型：
--
作者：
R. Wong;J. Joe;Se-Heon Kim;J. Shah;B. Horsburgh;Y. Fong
当直接递送至已形成的肿瘤时，溶瘤疱疹病毒在动物模型中具有显着的抗肿瘤作用。淋巴转移是许多肿瘤类型的常见现象。本研究探讨了减毒、具有复制能力的溶瘤单纯疱疹病毒 (NV1023) 的潜力，既可以通过直接注射治疗原发性肿瘤，也可以通过淋巴系统治疗从原发性癌症部位排出淋巴液的淋巴结内的转移性肿瘤。将异硫蓝染料注入小鼠耳廓以确定正常的淋巴引流模式，并证明一组同侧颈部淋巴结的蓝色染色一致。通过 5-溴-4-氯-3-吲哚基-β-D-吡喃半乳糖苷组织化学和病毒斑块测定，耳部注射 NV1023 导致病毒转运至这些淋巴结。表达绿色荧光蛋白的溶瘤疱疹病毒（NV1066）也在荧光显微镜下证明病毒从耳廓转移到颈部淋巴结。使用 SCC VII 细胞系，开发了一种新型耳廓鳞状细胞癌小鼠模型，其颈淋巴结转移发生率约为 20%。切除耳廓 SCC VII 肿瘤后将 NV1023 或 NV1066 递送至手术床，导致颈部淋巴结内转移性 SCC VII 细胞成功病毒感染。 7 周随访后，NV1023 治疗显着增强了局部控制（p < 0.05，Fisher 精确检验）和无病生存（p < 0.05，对数秩检验）。这项研究表明，手术切除后将溶瘤疱疹病毒递送至原发肿瘤部位可能对减少原发部位复发和区域淋巴结转移具有显着影响。
Oncolytic herpesviruses have significant antitumoral effects in animal models when delivered directly to established tumors. Lymphatic metastases are a common occurrence for many tumor types. This study investigates the potential of an attenuated, replication-competent, oncolytic herpes simplex virus (NV1023) both to treat a primary tumor by direct injection and to travel through the lymphatic system to treat metastatic tumor within the lymph nodes draining lymph from the site of primary cancer. Isosulfan blue dye was injected into murine auricles to determine normal lymphatic drainage patterns and demonstrated consistent blue staining of a group of ipsilateral cervical lymph nodes. Auricular injections of NV1023 resulted in viral transit to these lymph nodes as measured by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside histochemistry and viral plaque assay. An oncolytic herpesvirus (NV1066) expressing green fluorescent protein also demonstrated viral transit from the auricle to the cervical lymph nodes on fluorescence microscopy. Using the SCC VII cell line, a novel murine model of auricular squamous cell carcinoma was developed with an approximately 20% incidence of cervical lymph node metastases. Delivery of NV1023 or NV1066 to the surgical beds after excision of auricular SCC VII tumors resulted in successful viral infection of metastatic SCC VII cells within the cervical lymph nodes. After a 7-week follow-up, significantly enhanced locoregional control (p < 0.05, Fisher exact test) and disease-free survival (p < 0.05, log rank test) were evident with NV1023 treatment. This study demonstrates that the delivery of an oncolytic herpesvirus to a primary tumor site after surgical excision may have a significant impact on reducing both primary site recurrence and regional nodal metastases.