The Hyaluronidase technology enhances the intratumoral spread of oncolytic viruses allowing the virus to destroy more effectively the tumors. Most tumors are formed by tumor cells and a significant part of accompanying tissue known as tumor stroma or desmoplasia. Such stroma limits the dissemination of chemotherapeutic drugs and oncolytic viruses. Expression of hyaluronidase from our oncolytic viruses degrades the tumor stroma and improves virus spread ( Guedan S et al., Mol Ther, 2010). Hyaluronidase technology is integrated in the first VCN lead candidate, VCN-01 which also shows enhanced tumor targeting. VCN Biosciences scientists have confirmed the good anti-tumor efficacy of VCN-01 after intravenous or intratumoral administration and a good safety and tolerability profile. (Rodríguez-García A et al., Clin Cancer Res, 2015). They have also showed that the combination of VCN-01 with first line treatments for pancreatic cancer, such as gemcitabine (extracted from Guinn BA et al., Human Gene Ther, 2014) or nab-paclitaxel/gemcitabine, results in enhanced anti-tumor activity in different pancreatic cancer models.
The therapeutic potential of oncolytic adenovirus including Hyaluronidase technology has also been validated on different indications, including brain tumors (Martinez-Quintanilla J et al., Mol Ther, 2015), glioma (Vera B et al., PLoS One 2016) and pediatric osteosarcoma (Martínez-Vélez N et al., Clin Cancer Res, 2016).
In addition VCN-01 given intravitreally has shown good anti-tumor activity in highly predictive retinoblastoma tumor models with good safety profile. These results enable translation of VCN-01 to the clinics for the treatment of retinoblastoma, with a phase I/II clinical trial expected to start in 2017.
Guedan S, Rojas JJ, Gros A, Mercade E, Cascallo M, Alemany R. "Hyaluronidase Expression by an Oncolytic Adenovirus Enhances Its Intratumoral Spread and Suppresses Tumor Growth". Molecular Therapy vol. 18 no. 7, 1275–1283 (2010).
Guinn BA, Braidwood L, Parker A, Peng KW, Seymour L. 8th International Conference on Oncolytic Virus Therapeutics. Human Gene Therapy. December 2014, 25(12): 1062-1084. doi:10.1089/hum.2014.118.
Rodríguez-García A, Giménez-Alejandre M, Rojas JJ, Moreno R, Bazan-Peregrino M, Cascalló M, Alemany R. Safety and efficacy of VCN-01, an oncolytic adenovirus combining fiber HSG-binding domain replacement with RGD and hyaluronidase expression. Clin Cancer Res. 2015 Mar 15;21(6):1406-18. doi: 10.1158/1078-0432.CCR-14-2213. Epub 2014 Nov 12.
Martinez-Quintanilla J, He D, Wakimoto H, Alemany R, Shah K. Mol Ther. 2015 Jan;23(1):108-18.
Vera B, Martínez-Vélez N, Xipell E, Acanda de la Rocha A, Patiño-García A, Saez-Castresana J, Gonzalez-Huarriz M, Cascallo M, Alemany R, Alonso MM. PLoS One. 2016 Jan 25;11(1)
Martínez-Vélez N, Xipell E, Vera B, Acanda de la Rocha A, Zalacain M, Marrodán L, Gonzalez-Huarriz M, Toledo G, Cascallo M, Alemany R, Patiño A, Alonso MM. Clin Cancer Res. 2016 May 1;22(9):2217-25