Herpes simplex virus type-1(HSV-1) oncolytic and highly fusogenic mutants carrying the NV1020 genomic deletion effectively inhibit primary and metastatic tumors in mice
| Autor: | Abolghasem Baghian, Vladimir N. Chouljenko, Konstantin G. Kousoulas, Michael T. Kearney, Anna Israyelyan, Andrew T David |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Lung Neoplasms
Mutagenesis (molecular biology technique) Mammary Neoplasms Animal Genome Viral Herpesvirus 1 Human Biology medicine.disease_cause Virus lcsh:Infectious and parasitic diseases 03 medical and health sciences Mice Viral Proteins 0302 clinical medicine Viral Envelope Proteins Virology medicine Escherichia coli Animals lcsh:RC109-216 030304 developmental biology Oncolytic Virotherapy Recombination Genetic 0303 health sciences Mutation Mice Inbred BALB C Cell fusion Research Mammary Neoplasms Experimental 3. Good health Oncolytic virus Disease Models Animal Herpes simplex virus Infectious Diseases 030220 oncology & carcinogenesis Cancer cell Vero cell Female |
| Zdroj: | Virology Journal Virology Journal, Vol 5, Iss 1, p 68 (2008) |
| ISSN: | 1743-422X |
| DOI: | 10.1186/1743-422x-5-68 |
| Popis: | Background The NV1020 oncolytic herpes simplex virus type-1 has shown significant promise for the treatment of many different types of tumors in experimental animal models and human trials. Previously, we described the construction and use of the NV1020-like virus OncSyn to treat human breast tumors implanted in nude mice. The syncytial mutation gKsyn1 (Ala-to-Val at position 40) was introduced into the OncSyn viral genome cloned into a bacterial artificial chromosome using double-red mutagenesis in E. coli to produce the OncdSyn virus carrying syncytial mutations in both gB(syn3) and gK(syn1). Results The OncdSyn virus caused extensive virus-induced cell fusion in cell culture. The oncolytic potential of the OncSyn and OncdSyn viruses was tested in the highly metastatic syngeneic mouse model system, which utilizes 4T1 murine mammary cancer cells implanted within the interscapular region of Balb/c mice. Mice were given three consecutive intratumor injections of OncSyn, OncdSyn, or phosphate buffered saline four days apart. Both OncSyn and OncdSyn virus injections resulted in significant reduction of tumor sizes (p < 0.05) compared to control tumors. Virus treated mice but not controls showed a marked reduction of metastatic foci in lungs and internal organs. Mouse weights were not significantly impacted by any treatment during the course of the entire study (p = 0.296). Conclusion These results show that the attenuated, but highly fusogenic OncSyn and OncdSyn viruses can effectively reduce primary and metastatic breast tumors in immuncompetent mice. The available bac-cloned OncSyn and OncdSyn viral genomes can be rapidly modified to express a number of different anti-tumor and immunomodulatory genes that can further enhance their anti-tumor potency. |
| Databáze: | OpenAIRE |
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