our science 01b



The Hyaluronidase technology enhances the intratumoural spread of oncolytic viruses allowing the virus to destroy more effectively the tumours. Most tumours are formed by tumour cells and a significant part of accompanying tissue known as tumour stroma or desmoplasia. Such stroma limits the dissemination of chemotherapeutic drugs and oncolytic viruses. Expression of hyaluronidase from our oncolytic viruses degrades the hyaluronic acid within the tumour 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 tumour targeting. VCN Biosciences scientists have confirmed the good anti-tumour efficacy of VCN-01 after intravenous or intratumoural 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 or nab-paclitaxel/gemcitabine, results in enhanced anti-tumour activity in different pancreatic cancer models. The therapeutic potential of oncolytic adenovirus expressing hyaluronidase has also been validated on different indications, including brain tumours (Martinez-Quintanilla J et al., Mol Ther, 2015),  glioma (Vera B et al., PLoS One 2016), pediatric osteosarcoma (Martínez-Vélez N et al., Clin Cancer Res, 2016) and retinoblastoma (Pascual-Pasto G et al., Science Translational Medicine  2019). 

 

VCN-01 is an oncolytic adenovirus designed to replicate in cancer cells with dysfunctional RB1 pathway, expose tumour neoantigens of lysed tumours, improve virus tumor targeting, express hyaluronidase to enhance virus intratumoural spreading and facilitate chemotherapy and immune cells extravasation into the tumor. VCN-01 is currently being tested in different clinical trials to test the mechanism of action, safety, tolerability and efficacy of the virus in different indications including  advanced pancreatic cancer (NCT02045589 and NCT02045602), retinoblastoma (NCT03284268) and Squamous Cell Carcinoma of the Head and Neck (NCT03799744). VCN-01 is being evaluated alone or in combination with chemotherapy and immune check point inhibitors. 

 



References:
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).
https://www.ncbi.nlm.nih.gov/pubmed/20442708

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.
http://clincancerres.aacrjournals.org/content/21/6/1406.long

Martinez-Quintanilla J, He D, Wakimoto H, Alemany R, Shah K. Encapsulated Stem Cells Loaded With Hyaluronidase-expressing Oncolytic Virus for Brain Tumor Therapy . Mol Ther. 2015 Jan;23(1):108-18.
https://www.ncbi.nlm.nih.gov/pubmed/25352242


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. Characterization of the Antiglioma Effect of the Oncolytic Adenovirus VCN-01 . PLoS One. 2016 Jan 25;11(1)
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147211>

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. The Oncolytic Adenovirus VCN-01 as Therapeutic Approach Against Pediatric Osteosarcoma. Clin Cancer Res. 2016 May 1;22(9):2217-25
http://clincancerres.aacrjournals.org/content/22/9/2217.long 

 

Pascual-Pasto G, Bazan-Peregrino M, Olaciregui NG, Restrepo-Perdomo CA, Mato-Berciano A, Ottaviani D Weber K, Correa G, Paco S Vila-Ubach M, Cuadrado-Vilanova M, Castillo-Ecija, Botteri G, Garcia-Gerique L, Moreno-Gilabert H, Gimenez-Alejandre M, Alonso-Lopez P, Farrera-Sal M, Torres-Manjon S, Ramos-Lozano D, Moreno R, Aerts I, Doz F, Cassoux N, Chapeaublanc E, Torrebadell M, Roldan M König A, Suñol M, Claverol J, Lavarino, Carmen de T, Fu L13, Radvanyi F, Munier FL, Catalá-Mora J, Mora J, Alemany R, Cascalló M, Chantada GL, Carcaboso AM. Therapeutic targeting of the RB1 pathway in retinoblastoma with the oncolytic adenovirus VCN-01. Science Translational Medicine  23 Jan 2019: Vol. 11, Issue 476, eaat9321. DOI: 10.1126/scitranslmed.aat9321 

https://stm.sciencemag.org/content/11/476/eaat9321.short