Combined used of virotherapy and immune checkpoint inhibitors (ICI) has arisen as a promising treatment for cancer. VCN-01 is a selective oncolytic adenovirus (OAd) with hyaluronidase activity that can enhance the activity of ICIs as it can potentially increase their extravasation. The aims of this project are: to demonstrate that VCN01 is able to increase both ICI extravasation and antitumour activity, and to generate new OAds with potentiated hyal-related mechanisms of action.
OAds were i.v. administered in NP-18 (PDL1+; human pancreatic cell line) xenograft male athymic mouse model. Fluorescently labelled anti-PD-L1 was used to assess its extravasation. TRAMP-C2 tumours were subcutaneously implanted in C57BL/6J. VCN01 was injected i.t alone or in combination with 5 doses i.p. of anti-PD-L1 antibody. New OAds were generated with two different hyalorunidase genes (A and B). Different locations within the viral genome and different splicing acceptors to express these hyaluronidases were tested.
VCN-01 significantly increased the extravasation of anti-PD-L1 antibodies into NP-18 tumours compared to a control oncolytic adenovirus ICOVIR15K and to control group, due to VCN-01’s capability to express hyaluronidase. Administration of VCN-01 within subcutaneous TRAMP-C2 tumours, alone or in combination with anti-PD-L1 antibody showed anti-tumour activity when compared with PBS or anti-PD-L1 treated tumours. The combined treatment showed increased anti-tumour activity, but not significant, when compared to VCN-01 alone. Most of the new hyal-OAds presented attenuated tumour cytotoxicity in vitro compared to VCN-01 except from VCNA and VCNB. Moreover, both candidates presented significantly higher hyalorunidase activity in vitro at 24h and 72h post infection compared to VCN-01.
VCN-01 enhances the extravasation of anti-PD-L1 to tumours. Combination of VCN-01 with anti-PD-L1 antibody significantly delayed tumour growth over time when compared with PBS or anti-PD-L1 treated tumours. VCNA and VCNB maintain tumour cytotoxicity and show higher hyaluronidase activity compared to VCN-01.
VCN Biosciences S.L.
VCN Biosciences S.L.
M. Farrera, A. Mato-Berciano, S. Morgado, S.L. M. Bazan-Peregrino: Employed by VCN Biosciences S.L. and presenting a company\'s product. R. Alemany: Founder and part of advisory board of VCN Biosciences. All other authors have declared no conflicts of interest.