Related Experiment Video
Updated: Oct 4, 2025
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
Published on: June 20, 2015
VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects
Miriam Bazan-Peregrino1, Rocio Garcia-Carbonero2, Berta Laquente3
1VCN Biosciences, Sant Cugat del Valles, Barcelona, 08174, Spain mbazan@vcnbiosciences.com mah4006@med.cornell.edu.
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 1×1011 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.
Trial Registration Number:
EudraCT number: 2012-005556-42 and NCT02045589.
Insights
VCN-01, an oncolytic adenovirus, effectively replicates in pancreatic cancer models, reducing tumor stroma and enhancing chemotherapy delivery. This novel agent shows promise for treating pancreatic ductal adenocarcinoma by disrupting dense tumors.
Area of Science:
- Oncolytic virotherapy
- Cancer biology
- Drug delivery systems
Background:
- Pancreatic ductal adenocarcinoma (PDAC) presents a therapeutic challenge due to its dense desmoplastic stroma, hindering drug penetration.
- VCN-01 is an oncolytic adenovirus engineered to replicate in cancer cells with RB1 pathway dysfunction and express hyaluronidase.
- The study investigates VCN-01's mechanism of action in preclinical models and PDAC patients.
Purpose of the Study:
- To evaluate the replication and antitumor efficacy of VCN-01.
- To assess VCN-01's ability to degrade tumor stroma and improve drug delivery.
- To determine the safety and preliminary efficacy of VCN-01 in a clinical trial for PDAC.
Main Methods:
- VCN-01 efficacy was tested in preclinical models (intravenous/intratumoral administration) with and without chemotherapy.
- Hyaluronidase activity was assessed via histochemical staining and drug delivery measurements.
- A proof-of-concept clinical trial administered VCN-01 intratumorally to PDAC patients, monitoring hyaluronidase levels and tumor stiffness.
Main Results:
- VCN-01 demonstrated replication and antitumor effects in PDAC models, enhanced by combination with chemotherapy.
- VCN-01-expressed hyaluronidase degraded tumor stroma, improving delivery of chemotherapy and antibodies.
- Clinical trials showed VCN-01 was well-tolerated, leading to disease stabilization and evidence of viral replication and stromal disruption.
Conclusions:
- VCN-01 exhibits direct antitumor activity and stromal disruption capabilities.
- VCN-01 represents a novel therapeutic strategy for cancers characterized by dense stromal tissue.
- The oncolytic adenovirus has potential as a new agent for treating PDAC.
