Related Experiment Video
Updated: Apr 19, 2026
Handling of the Cotton Rat in Studies for the Pre-clinical Evaluation of Oncolytic Viruses
Published on: November 24, 2014
A novel immunocompetent murine model for replicating oncolytic adenoviral therapy
L Zhang1, F Hedjran1, C Larson1
1Clinical Trials Office, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Abstract:
Oncolytic adenoviruses are under investigation as a promising novel strategy for cancer immunotherapeutics. Unfortunately, there is no immunocompetent mouse cancer model to test oncolytic adenovirus because murine cancer cells are generally unable to produce infectious viral progeny from human adenoviruses. We find that the murine K-ras-induced lung adenocarcinoma cell line ADS-12 supports adenoviral infection and generates infectious viral progeny. ADS-12 cells express the coxsackie and adenovirus receptor and infected ADS-12 cells express the viral protein E1A. We find that our previously described oncolytic virus, adenovirus TAV-255 (AdTAV-255), kills ADS-12 cells in a dose- and time-dependent manner. We investigated ADS-12 cells as an in-vivo model system for replicating oncolytic adenoviruses. Subcutaneous injection of ADS-12 cells into immunocompetent 129 mice led to tumor formation in all injected mice. Intratumoral injection of AdTAV-255 in established tumors causes a significant reduction in tumor growth. This model system represents the first fully immunocompetent mouse model for cancer treatment with replicating oncolytic adenoviruses, and therefore will be useful to study the therapeutic effect of oncolytic adenoviruses in general and particularly immunostimulatory viruses designed to evoke an antitumor immune response.
Insights
Researchers developed a new immunocompetent mouse model for oncolytic adenovirus therapy. This model utilizes a specific lung adenocarcinoma cell line that supports viral replication, enabling effective in-vivo testing of cancer immunotherapeutics.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Oncolytic adenoviruses show promise for cancer treatment.
- Existing immunocompetent mouse models are limited for studying human adenovirus replication in murine cancer cells.
Purpose of the Study:
- To establish a novel immunocompetent mouse model for evaluating replicating oncolytic adenoviruses.
- To demonstrate the utility of the ADS-12 cell line and AdTAV-255 in this model.
Main Methods:
- Characterized the murine lung adenocarcinoma cell line ADS-12 for adenoviral infection and progeny production.
- Utilized subcutaneous injection of ADS-12 cells in 129 mice to create tumors.
- Administered intratumoral injection of adenovirus TAV-255 (AdTAV-255) into established tumors.
Main Results:
- ADS-12 cells support human adenovirus infection and generate infectious viral progeny.
- AdTAV-255 demonstrated dose- and time-dependent killing of ADS-12 cells in vitro.
- Intratumoral AdTAV-255 injection significantly reduced tumor growth in the established ADS-12 mouse model.
Conclusions:
- The ADS-12 cell line in immunocompetent mice provides the first fully functional model for studying replicating oncolytic adenoviruses.
- This model is crucial for advancing the therapeutic development of oncolytic adenoviruses, especially immunostimulatory agents.
More Related Videos
07:13Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
Published on: March 26, 2014
09:16Ex Vivo Organoid Model of Adenovirus-Cre Mediated Gene Deletions in Mouse Urothelial Cells
Published on: May 5, 2022
