Please use this identifier to cite or link to this item:
https://hdl.handle.net/2445/181698
Title: | VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects |
Author: | Bazan Peregrino, Miriam Garcia Carbonero, Rocio Laquente, Berta Álvarez, Rafael Mato Berciano, Ana Gimenez Alejandre, Marta Morgado, Sara Rodríguez García, Alba Maliandi, Maria V. Riesco, M. Carmen Moreno Olié, Rafael Ginestà, Mireia M. Perez Carreras, Mercedes Gornals Soler, Joan B. Prados, Susana Perea, Sofía Capellá, G. (Gabriel) Alemany Bonastre, Ramon Salazar Soler, Ramón Blasi, Emma Blasco, Carmen Cascallo, Manel Hidalgo, Manuel |
Keywords: | Càncer de pàncrees Adenovirus Pancreas cancer Adenoviruses |
Issue Date: | 1-Nov-2021 |
Publisher: | BMJ |
Abstract: | Background Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense desmoplastic stroma that limits the delivery of anticancer agents. VCN-01 is an oncolytic adenovirus designed to replicate in cancer cells with a dysfunctional RB1 pathway and express hyaluronidase. Here, we evaluated the mechanism of action of VCN-01 in preclinical models and in patients with pancreatic cancer. Methods VCN-01 replication and antitumor efficacy were evaluated alone and in combination with standard chemotherapy in immunodeficient and immunocompetent preclinical models using intravenous or intratumoral administration. Hyaluronidase activity was evaluated by histochemical staining and by measuring drug delivery into tumors. In a proof-of-concept clinical trial, VCN-01 was administered intratumorally to patients with PDAC at doses up to 1x10(11) viral particles in combination with chemotherapy. Hyaluronidase expression was measured in serum by an ELISA and its activity within tumors by endoscopic ultrasound elastography. Results VCN-01 replicated in PDAC models and exerted antitumor effects which were improved when combined with chemotherapy. Hyaluronidase expression by VCN-01 degraded tumor stroma and facilitated delivery of a variety of therapeutic agents such as chemotherapy and therapeutic antibodies. Clinically, treatment was generally well-tolerated and resulted in disease stabilization of injected lesions. VCN-01 was detected in blood as secondary peaks and in post-treatment tumor biopsies, indicating virus replication. Patients had increasing levels of hyaluronidase in sera over time and decreased tumor stiffness, suggesting stromal disruption. Conclusions VCN-01 is an oncolytic adenovirus with direct antitumor effects and stromal disruption capabilities, representing a new therapeutic agent for cancers with dense stroma. |
Note: | Reproducció del document publicat a: https://doi.org/10.1136/jitc-2021-003254 |
It is part of: | Journal for Immunotherapy of Cancer, 2021, vol. 9, num. 11, p. e003254 |
URI: | https://hdl.handle.net/2445/181698 |
Related resource: | https://doi.org/10.1136/jitc-2021-003254 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
e003254.full.pdf | 1.77 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License