Establishment of a mouse melanoma model system for the efficient infection and replication of human adenovirus type
Sujin Kang1, Joo-Hang Kim2, So Young Kim1
1Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
Abstract:
Due to poor adenoviral infectivity and replication in mouse tumor cell types compared with human tumor cell types, use of human-type adenoviral vectors in mouse animal model systems was limited. Here, we demonstrate enhanced infectivity and productive replication of adenovirus in mouse melanoma cells following introduction of both the Coxsackievirus and adenovirus receptor (CAR) and E1B-55K genes. Introduction of CAR into B16BL6 or B16F10 cells increased the infectivity of GFP-expressing adenovirus; however, viral replication was unaffected. We demonstrated a dramatic increase of adenoviral replication (up to 100-fold) in mouse cells via E1B-55K expression and subsequent viral spreading in mouse tissue. These results reveal for the first time that human adenovirus type 5 (Ad5)-based oncolytic virus can be applied to immunocompetent mouse with the introduction of CAR and E1B-55K to syngenic mouse cell line.
Insights
Researchers enhanced adenovirus infectivity and replication in mouse melanoma cells by introducing the Coxsackievirus and adenovirus receptor (CAR) and E1B-55K genes. This advance enables the use of adenovirus-based oncolytic viruses in mouse models.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Viral vector development
Background:
- Adenoviral vectors exhibit limited infectivity and replication in mouse tumor cells compared to human cells.
- This limitation restricts the utility of human-type adenoviral vectors in preclinical mouse models.
Purpose of the Study:
- To enhance adenovirus infectivity and replication in mouse melanoma cells.
- To enable the application of human adenovirus type 5 (Ad5)-based oncolytic viruses in immunocompetent mouse models.
Main Methods:
- Introduction of the Coxsackievirus and adenovirus receptor (CAR) gene into mouse melanoma cell lines (B16BL6, B16F10).
- Introduction of the E1B-55K gene into mouse melanoma cells.
- Infection with GFP-expressing adenovirus and assessment of viral replication and spreading.
Main Results:
- CAR introduction enhanced adenovirus infectivity in mouse melanoma cells but did not affect viral replication.
- E1B-55K expression led to a significant increase (up to 100-fold) in adenoviral replication.
- Successful viral spreading in mouse tissue was observed after E1B-55K expression.
Conclusions:
- Co-introduction of CAR and E1B-55K genes significantly enhances adenovirus infectivity and replication in mouse cells.
- This strategy overcomes previous limitations, allowing the use of Ad5-based oncolytic viruses in immunocompetent mouse models.
- This breakthrough facilitates preclinical studies of oncolytic virotherapy in syngeneic mouse models.
