Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic metastases Journal Article
| Authors: | Wong, R. J.; Joe, J. K.; Kim, S. H.; Shah, J. P.; Horsburgh, B.; Fong, Y. |
| Article Title: | Oncolytic herpesvirus effectively treats murine squamous cell carcinoma and spreads by natural lymphatics to treat sites of lymphatic metastases |
| Abstract: | 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-β-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. |
| Keywords: | cancer survival; controlled study; unclassified drug; histopathology; squamous cell carcinoma; carcinoma, squamous cell; drug efficacy; nonhuman; follow up; methodology; lymph node metastasis; antineoplastic agent; lymph nodes; lymphatic metastasis; animal cell; mouse; animal; animals; mice; animal tissue; green fluorescent protein; cell line; animal model; antineoplastic activity; assay; histology; physiology; animalia; dna viruses; lymph node; gene therapy; oncolytic virus; herpes virus; herpesviridae; murinae; simplexvirus; fluorescence microscopy; virus infection; cervical lymph node; lymphatic drainage; nv 1023; mice, inbred c3h; nv 1066; virus plaque; c3h mouse; male; article; 5 bromo 4 chloro 3 indolyl beta dextro galactopyranoside; pyranoside; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; martes pennanti |
| Journal Title: | Human Gene Therapy |
| Volume: | 13 |
| Issue: | 10 |
| ISSN: | 1043-0342 |
| Publisher: | Mary Ann Liebert, Inc |
| Date Published: | 2002-07-01 |
| Start Page: | 1213 |
| End Page: | 1223 |
| Language: | English |
| DOI: | 10.1089/104303402320138998 |
| PUBMED: | 12133274 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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