Generation of oncolytic herpes simplex viruses (HSV) for cancer therapy. We generated recombinant viruses in which glycoprotein D of the viral envelope was modified by the insertion, in different positions, of a single chain antibody (scFv) to HER2 receptor, expressed in mammary and ovary carcinomas. We demonstrated these viruses are re-targeted to cells that express HER2 and unable to use Nectin1 and HVEM HSV natural receptor (full retargeting). The oncolytic viruses were effective in animal models of ovary and mammary tumors and of gliomas that overexpress HER2 receptor. In vivo experiments were carried out in collaboration with Prof. Lollini of the University of Bologna and with Dr. Malatesta of the University of Genova. Viruses retargeted to other tumor-specific receptors (PSMA, EGFR, EGFRvIII) have been engineered.
Viral evolution dynamics: Viruses evolve at a higher rate as compared to their host(s). Specific properties of the different viral replicative strategies and host-parasite interactions can drive or push viral evolution. Even viruses considered to be substantially stable can change, under selective pressure. The aim of the research is to follow, by means of molecular tools, in vitro viral evolution and to dissect the conditions which promote it.
