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Characterization of herpes simplex virus 1 strains as platforms for the development of oncolytic viruses against liver cancer
Author(s) -
Argnani Rafaela,
Marconi Peggy,
Volpi Ilaria,
Bolanos Elixabet,
Carro Elvira,
Ried Christine,
Santamaria Enrique,
Pourchet Aldo,
Epstein Alberto L.,
Brocker Thomas,
Corrales Fernando Jose,
Manservigi Roberto,
Goicoechea Ibai,
Foschini Mariagiovanna,
HernandezAlcoceba Ruben
Publication year - 2011
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02628.x
Subject(s) - oncolytic virus , herpes simplex virus , biology , virology , bioluminescence imaging , virus , virotherapy , immunogenicity , transgene , luciferase , microbiology and biotechnology , antibody , cell culture , immunology , gene , transfection , biochemistry , genetics
Background Diverse oncolytic viruses ( OV ) are being designed for the treatment of cancer. The characteristics of the parental virus strains may influence the properties of these agents. Aims To characterize two herpes simplex virus 1 strains ( HSV ‐1 17syn + and HFEM ) as platforms for virotherapy against liver cancer. Methods The luciferase reporter gene was introduced in the intergenic region 20 locus of both HSV ‐1 strains, giving rise to the Cgal‐Luc and H6‐Luc viruses. Their properties were studied in hepatocellular carcinoma ( HCC ) cells in vitro . Biodistribution was monitored by bioluminescence imaging ( BLI ) in athymic mice and immune‐competent B ab/c mice. Immunogenicity was studied by MHC ‐tetramer staining, in vivo killing assays and determination of specific antibody production. Intratumoural transgene expression and oncolytic effect were studied in HuH‐7 xenografts. Results The H6‐Luc virus displayed a syncytial phenotype and showed higher cytolytic effect on some HCC cells. Upon intravenous or intrahepatic injection in mice, both viruses showed a transient transduction of the liver with rapid relocalization of bioluminescence in adrenal glands, spinal cord, uterus and ovaries. No significant differences were observed in the immunogenicity of these viruses. Local intratumoural administration caused progressive increase in transgene expression during the first 5 days and persisted for at least 2 weeks. H6‐Luc achieved faster amplification of transgene expression and stronger inhibition of tumour growth than Cgal‐Luc , although toxicity of these non‐attenuated viruses should be reduced to obtain a therapeutic effect. Conclusions The syncytial H6‐Luc virus has a strong oncolytic potential on human HCC xenografts and could be the basis for potent OV .