Related Experiment Video
Updated: Jun 25, 2025
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Is oncolytic adenoviral-mediated immunotherapy through p53-overexpression the solution to refractory pancreatic
Lucy J A Harriss1, Lewis Stevens2, Charles J Rayner3
1Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Abstract:
Evaluation of: Araki H, Tazawa H, Kanaya N, et al. Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer. Mol Ther Oncolytics. 2022;27:3-13.Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. PDAC has a dense, desmoplastic stroma and immunosuppressive microenvironment, which impedes current treatment options. Immunotherapy delivered via oncolytic virotherapy is one potential solution to these barriers. Immune checkpoint inhibitors may facilitate immunogenic cell death by improving immune cell infiltration in cancer cells. PD-1 blockade shows better clinical outcomes for certain cancers. The addition of p53 to stimulate cell cycle arrest remains a novel field of research. The evaluated article by Araki et al. explores the efficacy of PD-1 blockade with oncolytic adenovirus platforms on immunogenic cell death and the possibility of combining PD-1 blockade and p53-activation. In vitro analysis showed increased cell death in multiple cell lines infected with AdV mediating p53 expression. The underlying process may attribute to apoptosis and autophagy, with evidence of increased immunogenic cell death. In vivo models demonstrated improved efficacy of p53-expressing AdV, particularly with the addition of PD-1 blockade which appears to be related to CD8+ cell infiltration.
Insights
Oncolytic adenovirus therapy with p53 overexpression enhanced cancer cell death and improved PD-1 blockade efficacy in pancreatic cancer models. This combination therapy promoted immunogenic cell death and increased CD8+ T cell infiltration.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Molecular oncology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) presents a poor prognosis due to its dense stroma and immunosuppressive microenvironment.
- Oncolytic viruses and immune checkpoint inhibitors (ICIs) like PD-1 blockade are promising therapeutic strategies for PDAC.
- Activating p53, a tumor suppressor, alongside these therapies is an emerging area of research.
Purpose of the Study:
- To evaluate the efficacy of oncolytic adenovirus (AdV) mediating p53 expression in pancreatic cancer.
- To assess the combination of p53-expressing AdV with PD-1 blockade.
- To investigate the impact on immunogenic cell death and anti-tumor immune responses.
Main Methods:
- In vitro studies using pancreatic cancer cell lines infected with p53-expressing AdV.
- In vivo studies using preclinical models of pancreatic cancer.
- Analysis of cell death mechanisms (apoptosis, autophagy) and immune cell infiltration (CD8+ T cells).
Main Results:
- p53-expressing AdV induced significant cancer cell death in vitro, associated with apoptosis and autophagy.
- Increased markers of immunogenic cell death were observed.
- In vivo, p53-expressing AdV demonstrated improved anti-tumor efficacy, which was further enhanced by PD-1 blockade, correlating with increased CD8+ T cell infiltration.
Conclusions:
- Oncolytic adenovirus-mediated p53 overexpression can promote immunogenic cell death in pancreatic cancer.
- Combining p53-expressing AdV with PD-1 blockade significantly enhances anti-tumor efficacy.
- This combination strategy holds potential for improving treatment outcomes in pancreatic cancer by modulating the tumor microenvironment and immune response.
More Related Videos
07:08Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets
Published on: February 2, 2024
08:35Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles
Published on: January 4, 2012
Related Concept Videos
01:27Tumor Immunotherapy
02:23Abnormal Proliferation