HSV as A Platform for the Generation of Retargeted, Armed, and Reporter-Expressing Oncolytic Viruses

Autor: Biljana Petrovic, Valentina Gatta, Gabriella Campadelli-Fiume, Elisa Avitabile, Paolo Malatesta, Laura Menotti
Přispěvatelé: Menotti, Laura, Avitabile, Elisa, Gatta, Valentina, Malatesta, Paolo, Petrovic, Biljana, Campadelli-Fiume, Gabriella
Rok vydání: 2018
Předmět:
0301 basic medicine
Glutamate Carboxypeptidase II
lcsh:QR1-502
retargeting
oncolytic herpesvirus
PSMA
EGFR
EGFRvIII
mIL12
Gaussia Luciferase
HER2
Gene Expression
oncolytic herpesvirus
Virus Replication
lcsh:Microbiology
law.invention
Mice
0302 clinical medicine
law
Genes
Reporter
Chlorocebus aethiops
Gene Order
Simplexvirus
Epidermal growth factor receptor
Transgenes
Interleukin-12
3. Good health
ErbB Receptors
Oncolytic Viruses
Infectious Diseases
030220 oncology & carcinogenesis
Antigens
Surface
Gene Targeting
Recombinant DNA
Genetic Engineering
EGFRvIII
EGFR
Genetic Vectors
Biology
Article
03 medical and health sciences
Gaussia
Gaussia Luciferase
Virology
Cell Line
Tumor
HER2
PSMA
Animals
Humans
mIL12
Luciferase
oncolytic herpesviru
Tropism
retargeting
biology.organism_classification
Oncolytic virus
Viral Tropism
030104 developmental biology
Viral replication
Mutation
Tissue tropism
biology.protein
Zdroj: Viruses
Volume 10
Issue 7
Viruses, Vol 10, Iss 7, p 352 (2018)
ISSN: 1999-4915
Popis: Previously, we engineered oncolytic herpes simplex viruses (o-HSVs) retargeted to the HER2 (epidermal growth factor receptor 2) tumor cell specific receptor by the insertion of a single chain antibody (scFv) to HER2 in gD, gH, or gB. Here, the insertion of scFvs to three additional cancer targets&mdash
EGFR (epidermal growth factor receptor), EGFRvIII, and PSMA (prostate specific membrane antigen)&mdash
in gD &Delta
6&ndash
38 enabled the generation of specifically retargeted o-HSVs. Viable recombinants resulted from the insertion of an scFv in place of aa 6&ndash
38, but not in place of aa 61&ndash
218. Hence, only the gD N-terminus accepted all tested scFv inserts. Additionally, the insertion of mIL12 in the US1-US2 intergenic region of the HER2- or EGFRvIII-retargeted o-HSVs, and the further insertion of Gaussia Luciferase, gave rise to viable recombinants capable of secreting the cytokine and the reporter. Lastly, we engineered two known mutations in gB
they increased the ability of an HER2-retargeted recombinant to spread among murine cells. Altogether, current data show that the o-HSV carrying the aa 6&ndash
38 deletion in gD serves as a platform for the specific retargeting of o-HSV tropism to a number of human cancer targets, and the retargeted o-HSVs serve as simultaneous vectors for two molecules.
Databáze: OpenAIRE
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