{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:29:28Z","timestamp":1790260168870,"version":"4.1.0"},"reference-count":87,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T00:00:00Z","timestamp":1456444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Most of the oncolytic herpes simplex viruses (HSVs) exhibit a high safety profile achieved through attenuation. They carry defects in virulence proteins that antagonize host cell response to the virus, including innate response, apoptosis, authophagy, and depend on tumor cell proliferation. They grow robustly in cancer cells, provided that these are deficient in host cell responses, which is often the case. To overcome the attenuation limits, a strategy is to render the virus highly cancer-specific, e.g., by retargeting their tropism to cancer-specific receptors, and detargeting from natural receptors. The target we selected is HER-2, overexpressed in breast, ovarian and other cancers. Entry of wt-HSV requires the essential glycoproteins gD, gH\/gL and gB. Here, we reviewed that oncolytic HSV retargeting was achieved through modifications in gD: the addition of a single-chain antibody (scFv) to HER-2 coupled with appropriate deletions to remove part of the natural receptors\u2019 binding sites. Recently, we showed that also gH\/gL can be a retargeting tool. The insertion of an scFv to HER-2 at the gH N-terminus, coupled with deletions in gD, led to a recombinant capable to use HER-2 as the sole receptor. The retargeted oncolytic HSVs can be administered systemically by means of carrier cells-forcedly-infected mesenchymal stem cells. Altogether, the retargeted oncolytic HSVs are highly cancer-specific and their replication is not dependent on intrinsic defects of the tumor cells. They might be further modified to express immunomodulatory molecules.<\/jats:p>","DOI":"10.3390\/v8030063","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T10:23:39Z","timestamp":1456482219000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Retargeting Strategies for Oncolytic Herpes Simplex Viruses"],"prefix":"10.3390","volume":"8","author":[{"given":"Gabriella","family":"Campadelli-Fiume","sequence":"first","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1312-8842","authenticated-orcid":false,"given":"Biljana","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Leoni","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Gianni","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costanza","family":"Casiraghi","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Gatta","sequence":"additional","affiliation":[{"name":"Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna 40126, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1126\/science.1851332","article-title":"Experimental therapy of human glioma by means of a genetically engineered virus mutant","volume":"252","author":"Martuza","year":"1991","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ilkow, C.S., Swift, S.L., Bell, J.C., and Diallo, J.S. (2014). From scourge to cure: Tumour-selective viral pathogenesis as a new strategy against cancer. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003836"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1126\/science.2173860","article-title":"Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture","volume":"250","author":"Chou","year":"1990","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/bjc.1996.431","article-title":"Selective in vitro replication of herpes simplex virus type 1 (HSV-1) ICP34.5 null mutants in primary human CNS tumours\u2014Evaluation of a potentially effective clinical therapy","volume":"74","author":"McKie","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/nm0995-938","article-title":"Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas","volume":"1","author":"Mineta","year":"1995","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/s00705-002-0944-x","article-title":"Oncolytic viral therapy using a spontaneously generated herpes simplex virus type 1 variant for disseminated peritoneal tumor in immunocompetent mice","volume":"148","author":"Takakuwa","year":"2003","journal-title":"Arch. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6737","DOI":"10.1158\/1078-0432.CCR-06-0759","article-title":"A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor","volume":"12","author":"Hu","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1245\/s10434-009-0809-6","article-title":"Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma","volume":"17","author":"Kaufman","year":"2010","journal-title":"Ann. Surg. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5763","DOI":"10.1200\/JCO.2009.24.3675","article-title":"Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma","volume":"27","author":"Senzer","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4005","DOI":"10.1158\/1078-0432.CCR-10-0196","article-title":"Phase I\/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III\/IV squamous cell cancer of the head and neck","volume":"16","author":"Harrington","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/mt.2008.228","article-title":"Phase Ib trial of mutant herpes simplex virus G207 inoculated pre- and post-tumor resection for recurrent GBM","volume":"17","author":"Markert","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/sj.gt.3301205","article-title":"Conditionally replicating herpes simplex virus mutant, g207 for the treatment of malignant glioma: Results of a phase I trial","volume":"7","author":"Markert","year":"2000","journal-title":"Gene Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/hed.20840","article-title":"Potential for efficacy of the oncolytic herpes simplex virus 1716 in patients with oral squamous cell carcinoma","volume":"30","author":"Mace","year":"2008","journal-title":"Head Neck"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0140-6736(00)04048-4","article-title":"Intralesional injection of herpes simplex virus 1716 in metastatic melanoma","volume":"357","author":"MacKie","year":"2001","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/mt.2008.240","article-title":"A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer","volume":"17","author":"Fong","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/cgt.2010.65","article-title":"A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer","volume":"18","author":"Nakao","year":"2011","journal-title":"Cancer Gene Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1245\/ASO.2006.08.035","article-title":"Pilot study of oncolytic viral therapy using mutant herpes simplex virus (HF10) against recurrent metastatic breast cancer","volume":"13","author":"Kimata","year":"2006","journal-title":"Ann. Surg. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1080\/00016480600702100","article-title":"Intratumoral injection of herpes simplex virus HF10 in recurrent head and neck squamous cell carcinoma","volume":"126","author":"Fujimoto","year":"2006","journal-title":"Acta Oto-Laryngol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrmicro3140","article-title":"New viruses for cancer therapy: Meeting clinical needs","volume":"12","author":"Miest","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/nbt.2287","article-title":"Oncolytic virotherapy","volume":"30","author":"Russell","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cripe, T.P., Chen, C.Y., Denton, N.L., Haworth, K.B., Hutzen, B., Leddon, J.L., Streby, K.A., Wang, P.Y., Markert, J.M., and Waters, A.M. (2015). Pediatric cancer gone viral. Part I: Strategies for utilizing oncolytic herpes simplex virus-1 in children. Mol. Ther. Oncolytics, 2.","DOI":"10.1038\/mto.2015.15"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.4049\/jimmunol.160.9.4457","article-title":"In situ cancer vaccination: An IL-12 defective vector\/replication-competent herpes simplex virus combination induces local and systemic antitumor activity","volume":"160","author":"Toda","year":"1998","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/sj.gt.3300550","article-title":"Treatment of intracranial gliomas in immunocompetent mice using herpes simplex viruses that express murine interleukins","volume":"5","author":"Andreansky","year":"1998","journal-title":"Gene Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1073\/pnas.040557897","article-title":"Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors","volume":"97","author":"Parker","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/sj.gt.3301885","article-title":"ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties","volume":"10","author":"Liu","year":"2003","journal-title":"Gene Ther."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Andtbacka, R.H., Kaufman, H.L., Collichio, F., Amatruda, T., Senzer, N., Chesney, J., Delman, K.A., Spitler, L.E., Puzanov, I., and Agarwala, S.S. (2015). Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol.","DOI":"10.1200\/JCO.2014.58.3377"},{"key":"ref_27","unstructured":"Fda.gov\/newsevents\/newsroom\/pressannouncements. Available online: http:\/\/www.webcitation.org\/6drvCltG7."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9683","DOI":"10.1128\/JVI.72.12.9683-9697.1998","article-title":"Recombinant herpes simplex virus type 1 engineered for targeted binding to erythropoietin receptor-bearing cells","volume":"72","author":"Laquerre","year":"1998","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.coviro.2011.12.001","article-title":"Viral and cellular contributions to herpes simplex virus entry into the cell","volume":"2","author":"Menotti","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/nrmicro2548","article-title":"Fusing structure and function: A structural view of the herpesvirus entry machinery","volume":"9","author":"Connolly","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/rmv.546","article-title":"The multipartite system that mediates entry of herpes simplex virus into the cell","volume":"17","author":"Amasio","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22635","DOI":"10.1073\/pnas.1011507107","article-title":"Structure of a core fragment of glycoprotein H from pseudorabies virus in complex with antibody","volume":"107","author":"Backovic","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/nsmb.1837","article-title":"Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL","volume":"17","author":"Chowdary","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/sj.embor.7400807","article-title":"Molecular gymnastics at the herpesvirus surface","volume":"7","author":"Rey","year":"2006","journal-title":"EMBO Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9992","DOI":"10.1128\/JVI.72.12.9992-10002.1998","article-title":"The ectodomain of a novel member of the immunoglobulin subfamily related to the poliovirus receptor has the attributes of a bona fide receptor for herpes simplex virus types 1 and 2 in human cells","volume":"72","author":"Cocchi","year":"1998","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1126\/science.280.5369.1618","article-title":"Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor","volume":"280","author":"Geraghty","year":"1998","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0092-8674(00)80058-6","article-title":"A novel role for 3-o-sulfated heparan sulfate in herpes simplex virus 1 entry","volume":"99","author":"Shukla","year":"1999","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0092-8674(00)81363-X","article-title":"Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF\/NGF receptor family","volume":"87","author":"Montgomery","year":"1996","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1097-2765(01)00298-2","article-title":"Herpes simplex virus glycoprotein D bound to the human receptor HveA","volume":"8","author":"Carfi","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4144","DOI":"10.1038\/sj.emboj.7600875","article-title":"Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry","volume":"24","author":"Krummenacher","year":"2005","journal-title":"EMBO J."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Di Giovine, P., Settembre, E.C., Bhargava, A.K., Luftig, M.A., Lou, H., Cohen, G.H., Eisenberg, R.J., Krummenacher, C., and Carfi, A. (2011). Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1. PLoS Pathog., 7.","DOI":"10.2210\/pdb3sku\/pdb"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4720","DOI":"10.1128\/JVI.78.9.4720-4729.2004","article-title":"The herpes simplex virus JMP mutant enters receptor-negative J cells through a novel pathway independent of the known receptors nectin1, HveA, and nectin2","volume":"78","author":"Cocchi","year":"2004","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9323","DOI":"10.1073\/pnas.0503907102","article-title":"The pro-fusion domain of herpes simplex virus glycoprotein D (gD) interacts with the gD N terminus and is displaced by soluble forms of viral receptors","volume":"102","author":"Fusco","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E3901","DOI":"10.1073\/pnas.1506846112","article-title":"Dissociation of HSV gL from gH by \u03b1v\u03b26- or \u03b1v\u03b28-integrin promotes gH activation and virus entry","volume":"112","author":"Gianni","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Atanasiu, D., Cairns, T.M., Whitbeck, J.C., Saw, W.T., Rao, S., Eisenberg, R.J., and Cohen, G.H. (2013). Regulation of herpes simplex virus gB-induced cell-cell fusion by mutant forms of gH\/gL in the absence of gD and cellular receptors. MBio, 4.","DOI":"10.1128\/mBio.00046-13"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"29993","DOI":"10.1074\/jbc.M803092200","article-title":"Analysis of a membrane interacting region of herpes simplex virus type 1 glycoprotein H","volume":"283","author":"Galdiero","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5508","DOI":"10.1073\/pnas.0601258103","article-title":"Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL-13\u03b12 receptor","volume":"103","author":"Zhou","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15124","DOI":"10.1073\/pnas.232588699","article-title":"Engineered herpes simplex virus 1 is dependent on IL13R\u03b12 receptor for cell entry and independent of glycoprotein D receptor interaction","volume":"99","author":"Zhou","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1073\/pnas.0611565104","article-title":"Separation of receptor binding and pro-fusogenic domains of glycoprotein D of herpes simplex virus 1 into distinct interacting proteins","volume":"104","author":"Zhou","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10153","DOI":"10.1128\/JVI.01133-08","article-title":"Construction of a fully retargeted herpes simplex virus 1 recombinant capable of entering cells solely via human epidermal growth factor receptor 2","volume":"20","author":"Menotti","year":"2008","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jackson, C., Browell, D., Gautrey, H., and Tyson-Capper, A. (2013). Clinical significance of HER-2 splice variants in breast cancer progression and drug resistance. Int. J. Cell Biol.","DOI":"10.1155\/2013\/973584"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1128\/JVI.02725-05","article-title":"A herpes simplex virus recombinant that exhibits a single-chain antibody to HER2\/neu enters cells through the mammary tumor receptor, independently of the gD receptors","volume":"80","author":"Menotti","year":"2006","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9039","DOI":"10.1073\/pnas.0812268106","article-title":"Inhibition of human tumor growth in mice by an oncolytic herpes simplex virus designed to target solely HER-2-positive cells","volume":"106","author":"Menotti","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"35186","DOI":"10.1074\/jbc.M604127200","article-title":"PEGylation and multimerization of the Anti-p185HER-2 single chain Fv fragment 4D5: Effects on tumor targeting","volume":"281","author":"Kubetzko","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Nanni, P., Gatta, V., Menotti, L., de Giovanni, C., Ianzano, M., Palladini, A., Grosso, V., Dall\u2019ora, M., Croci, S., and Nicoletti, G. (2013). Preclinical therapy of disseminated HER-2+ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003155"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/mt.2012.22","article-title":"Replication-competent herpes simplex virus retargeted to HER2 as therapy for high-grade glioma","volume":"20","author":"Gambini","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"34774","DOI":"10.18632\/oncotarget.5793","article-title":"Systemic delivery of HER2-retargeted oncolytic-HSV by mesenchymal stromal cells protects from lung and brain metastases","volume":"6","author":"Leoni","year":"2015","journal-title":"Oncotarget"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/mt.2012.211","article-title":"Effective treatment of an orthotopic xenograft model of human glioblastoma using an EGFR-retargeted oncolytic herpes simplex virus","volume":"21","author":"Uchida","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nrmicro1927","article-title":"Reprogrammed viruses as cancer therapeutics: Targeted, armed and shielded","volume":"6","author":"Cattaneo","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nbt1060","article-title":"Rescue and propagation of fully retargeted oncolytic measles viruses","volume":"23","author":"Nakamura","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/mt.2013.16","article-title":"Darpin-targeting of measles virus: Unique bispecificity, effective oncolysis, and enhanced safety","volume":"21","author":"Friedrich","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3014","DOI":"10.1128\/JVI.73.4.3014-3022.1999","article-title":"Glycoprotein gL-independent infectivity of pseudorabies virus is mediated by a gD-gH fusion protein","volume":"73","author":"Klupp","year":"1999","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6731","DOI":"10.1128\/JVI.77.12.6731-6742.2003","article-title":"Structure-function analysis of herpes simplex virus type 1 gD and gH-gL: Clues from gDgH chimeras","volume":"77","author":"Cairns","year":"2003","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Gatta, V., Petrovic, B., and Campadelli-Fiume, G. (2015). The engineering of a novel ligand in gH confers to HSV an expanded tropism independent of gD activation by its receptors. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004907"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/sj.gt.3302636","article-title":"Enhanced therapeutic efficacy of G207 for the treatment of glioma through Musashi1 promoter retargeting of \u03b334.5-mediated virulence","volume":"13","author":"Kanai","year":"2006","journal-title":"Gene Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/mt.2010.26","article-title":"Transcriptional and translational dual-regulated oncolytic herpes simplex virus type 1 for targeting prostate tumors","volume":"18","author":"Lee","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1002\/jgm.1519","article-title":"Novel tumour-specific promoters for transcriptional targeting of hepatocellular carcinoma by herpes simplex virus vectors","volume":"12","author":"Foka","year":"2010","journal-title":"J. Gene Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/cgt.2010.62","article-title":"Development of an oncolytic herpes simplex virus using a tumor-specific HIF-responsive promoter","volume":"18","author":"Longo","year":"2011","journal-title":"Cancer Gene Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/mt.2014.177","article-title":"Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV","volume":"23","author":"Mazzacurati","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.coviro.2015.06.005","article-title":"From virotherapy to oncolytic immunotherapy: Where are we now?","volume":"13","author":"Coffin","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9371","DOI":"10.1158\/0008-5472.CAN-07-0674","article-title":"Systemic therapy of spontaneous prostate cancer in transgenic mice with oncolytic herpes simplex viruses","volume":"67","author":"Varghese","year":"2007","journal-title":"Cancer Res."},{"key":"ref_72","first-page":"2306","article-title":"Potent systemic antitumor activity from an oncolytic herpes simplex virus of syncytial phenotype","volume":"62","author":"Fu","year":"2002","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/cgt.2008.83","article-title":"Comparison of intravenous vs. intraperitoneal administration of oncolytic herpes simplex virus 1 for peritoneal carcinomatosis in mice","volume":"16","author":"Kulu","year":"2009","journal-title":"Cancer Gene Ther."},{"key":"ref_74","first-page":"757","article-title":"Oncolytic herpes simplex virus treatment of metastatic breast cancer","volume":"40","author":"Wang","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1089\/hum.2006.17.1214","article-title":"Phase I, open-label, dose-escalating study of a genetically engineered herpes simplex virus, NV1020, in subjects with metastatic colorectal carcinoma to the liver","volume":"17","author":"Kemeny","year":"2006","journal-title":"Hum. Gene Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1200\/jco.2009.27.15_suppl.4089","article-title":"Phase II efficacy results using an oncolytic herpes simplex virus (NV1020) in patients with colorectal cancer metastatic to liver (mCRC)","volume":"27","author":"Geevarghese","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_77","first-page":"380","article-title":"The utility of cells as vehicles for oncolytic virus therapies","volume":"10","author":"Russell","year":"2008","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/gt.2008.45","article-title":"Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth","volume":"15","author":"Munguia","year":"2008","journal-title":"Gene Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/mt.2009.194","article-title":"Cell carriers for oncolytic viruses: Fed Ex for cancer therapy","volume":"17","author":"Willmon","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_80","first-page":"1523","article-title":"Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer","volume":"5","author":"Coukos","year":"1999","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1002\/ijc.29442","article-title":"Engineered adenoviruses combine enhanced oncolysis with improved virus production by mesenchymal stromal carrier cells","volume":"13","author":"Hammer","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1038\/mt.2014.118","article-title":"Cytokine conditioning enhances systemic delivery and therapy of an oncolytic virus","volume":"22","author":"Ilett","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1021\/mp200649g","article-title":"Vitamin D3-inducible mesenchymal stem cell-based delivery of conditionally replicating adenoviruses effectively targets renal cell carcinoma and inhibits tumor growth","volume":"9","author":"Hsiao","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1182\/blood-2013-09-528851","article-title":"Human mesenchymal stromal cells deliver systemic oncolytic measles virus to treat acute lymphoblastic leukemia in the presence of humoral immunity","volume":"123","author":"Castleton","year":"2014","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Duebgen, M., Martinez-Quintanilla, J., Tamura, K., Hingtgen, S., Redjal, N., Wakimoto, H., and Shah, K. (2014). Stem cells loaded with multimechanistic oncolytic herpes simplex virus variants for brain tumor therapy. J. Natl. Cancer Inst., 106.","DOI":"10.1093\/jnci\/dju090"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/cgt.2010.53","article-title":"Carrier cell-based delivery of replication-competent HSV-1 mutants enhances antitumor effect for ovarian cancer","volume":"18","author":"Fujiwara","year":"2011","journal-title":"Cancer Gene Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.cytogfr.2010.02.004","article-title":"Directing systemic oncolytic viral delivery to tumors via carrier cells","volume":"21","author":"Nakashima","year":"2010","journal-title":"Cytokine Growth Factor Rev."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/8\/3\/63\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:19:45Z","timestamp":1760210385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/8\/3\/63"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,26]]},"references-count":87,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3]]}},"alternative-id":["v8030063"],"URL":"https:\/\/doi.org\/10.3390\/v8030063","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,26]]}}}