2026-06-08T03:08:07Zhttps://docta.ucm.es/rest/oai/requestoai:docta.ucm.es:20.500.14352/1171722025-03-05T18:25:25Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense
author
Bazan-Peregrino, Miriam
author
García Carbonero, Rocío
author
Hidalgo, Manuel
2025-01-30T10:39:48Z
2025-01-30T10:39:48Z
2021
Bazan-Peregrino M, Garcia-Carbonero R, Laquente B, Álvarez R, Mato-Berciano A, Gimenez-Alejandre M, Morgado S, Rodríguez-García A, Maliandi MV, Riesco MC, Moreno R, Ginestà MM, Perez-Carreras M, Gornals JB, Prados S, Perea S, Capella G, Alemany R, Salazar R, Blasi E, Blasco C, Cascallo M, Hidalgo M. VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects. J Immunother Cancer. 2021 Nov;9(11):e003254. doi: 10.1136/jitc-2021-003254. PMID: 35149591; PMCID: PMC8578996.
2051-1426
10.1136/jitc-2021-003254
https://hdl.handle.net/20.500.14352/117172
https://doi.org/10.1136/jitc-2021-003254
35149591
https://pubmed.ncbi.nlm.nih.gov/35149591/
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 1×1011viral 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.
Trial registration number
EudraCT number: 2012-005556-42 andNCT02045589.
eng
Attribution-NonCommercial 4.0 International
VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects
journal article
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URL
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File
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f40ae56f281b99309ffcb8dcf3007a55
1818936
application/pdf
Bazan-Peregrino-2021-VCN-01 disrupts pancreati.pdf