*3.2. The Retargeted oHSVs are a Platform*

TAAs constitutes a family of molecules, with varying degrees of cancer specificity. Very often, the encoding genes are genetically amplified in cancer cells, such that the TAAs are overexpressed in cancer cells, and poorly or not expressed in non-cancerous cells. Many are located on the cell surface. Since each member of the family is expressed

across several cancer types [48], a single retargeted oHSV can potentially be employed against a number of different cancers. In most of our studies we selected HER2, expressed and amplified in a number of cancers, including breast, ovary, stomach, lung and pancreas cancers and glioblastoma, and is a relevant target in cancer immunotherapy. Thus, a HER2-retargeted oHSV can potentially be employed against a variety of indications. Glorioso laboratory, as well as our additionally generated oHSVs retargeted to EGFR, EpCAM, EGFRVIII specific for glioblastoma puntiforme, and PSMA, present in prostate cancers [23,26,49–51]. The EGFRVIII recombinant was further improved by insertion of a matrix metalloproteinase which enhanced intratumoral vector distribution and efficacy in a glioblastoma model [52]. Essentially, the retargeted oHSVs are a platform and can potentially be addressed to different TAAs. It is envisioned that the intensive molecular profiling programs carried out worldwide may lead to the discovery of novel TAAs, even more specific than the ones currently known.
