A novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer Journal Article
| Authors: | Gholami, S.; Marano, A.; Chen, N. G.; Aguilar, R. J.; Frentzen, A.; Chen, C. H.; Lou, E.; Fujisawa, S.; Eveno, C.; Belin, L.; Zanzonico, P.; Szalay, A.; Fong, Y. |
| Article Title: | A novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer |
| Abstract: | Vascular endothelial growth factor (VEGF) expression is higher in triple-negative breast cancers (TNBC) compared to other subtypes and is reported to predict incidence of distant metastases and shorter overall survival. We investigated the therapeutic impact of a vaccinia virus (VACV) GLV-1h164 (derived from its parent virus GLV-1h100), encoding a single-chain antibody (scAb) against VEGF (GLAF-2) in an orthotopic TNBC murine model. GLV-1h164 was tested against multiple TNBC cell lines. Viral infectivity, cytotoxicity, and replication were determined. Mammary fat pad tumors were generated in athymic nude mice using MDA-MB-231 cells. Xenografts were treated with GLV-1h164, GLV-1h100, or PBS and followed for tumor growth. Viral infectivity was time- and concentration-dependent. GLV-1h164 killed TNBC cell lines in a dose-dependent fashion with greater than 90 % cytotoxicity within 4 days at a multiplicity of infection of 5.0. In vitro, cytotoxicity of GLV-1h164 was identical to GLV-1h100. GLV-1h164 replicated efficiently in all cell lines with an over 400-fold increase in copy numbers from the initial viral dose within 4 days. In vivo, mean tumor volumes after 2 weeks of treatment were 73, 191, and 422 mm3 (GLV-1h164, GLV-1h100, and PBS, respectively) (p < 0.05). Both in vivo Doppler ultrasonography and immuno-staining showed decreased neo-angiogenesis in GLV-1h164-treated tumors compared to both GLV-1h100 and PBS controls (p < 0.05). This is the first study to demonstrate efficient combination of oncolytic and anti-angiogenic activity of a novel VACV on TNBC xenografts. Our results suggest that GLV-1h164 is a promising therapeutic agent that warrants testing for patients with TNBC. |
| Keywords: | immunohistochemistry; controlled study; unclassified drug; human cell; angiogenesis inhibitor; dose response; drug efficacy; nonhuman; mouse; animal tissue; tumor volume; animal experiment; animal model; in vivo study; antineoplastic activity; tumor xenograft; doppler echography; drug mechanism; oncolytic virus; vaccinia virus; drug cytotoxicity; virus replication; virus strain; antiangiogenic activity; anti-angiogenesis; concentration response; virus identification; growth inhibition; copy number variation; triple negative breast cancer; triple-negative breast cancer; virus infectivity; oncolytic viral therapy; human; female; article; glv-1h164; glv 1h164 |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 148 |
| Issue: | 3 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 2014-12-01 |
| Start Page: | 489 |
| End Page: | 499 |
| Language: | English |
| DOI: | 10.1007/s10549-014-3180-7 |
| PROVIDER: | scopus |
| PUBMED: | 25391896 |
| PMCID: | PMC5724036 |
| DOI/URL: | |
| Notes: | Erratum/Corrigendum issued, see PMID: 27026359 and DOI: 10.1007/s10549-016-3767-2 -- Export Date: 2 January 2015 -- Source: Scopus |
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