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Viruses 2018, 10(7), 352; https://doi.org/10.3390/v10070352

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

1
Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
2
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy
3
Department of Experimental Medicine, University of Genoa, Genoa 16132, Italy
4
Ospedale Policlinico San Martino—IRCCS per l’Oncologia, Genoa 16132, Italy
*
Author to whom correspondence should be addressed.
Received: 14 June 2018 / Revised: 25 June 2018 / Accepted: 26 June 2018 / Published: 30 June 2018
(This article belongs to the Section Animal Viruses)
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Abstract

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—EGFR (epidermal growth factor receptor), EGFRvIII, and PSMA (prostate specific membrane antigen)—in gD Δ6–38 enabled the generation of specifically retargeted o-HSVs. Viable recombinants resulted from the insertion of an scFv in place of aa 6–38, but not in place of aa 61–218. 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 6–38 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. View Full-Text
Keywords: retargeting; oncolytic herpesvirus; PSMA; EGFR; EGFRvIII; mIL12; Gaussia Luciferase; HER2 retargeting; oncolytic herpesvirus; PSMA; EGFR; EGFRvIII; mIL12; Gaussia Luciferase; HER2
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Menotti, L.; Avitabile, E.; Gatta, V.; Malatesta, P.; Petrovic, B.; Campadelli-Fiume, G. HSV as A Platform for the Generation of Retargeted, Armed, and Reporter-Expressing Oncolytic Viruses. Viruses 2018, 10, 352.

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