Establishment of a mouse melanoma model system for the efficient infection and replication of human adenovirus type 5-based oncolytic virus

• Mouse melanoma cells capable of adenoviral replication were designed.
• Introduction of CAR to mouse cell increased adenoviral infectivity.
• Introduction of E1B-55K to mouse cell increased adenoviral replication.
• Both of CAR and E1B-55K are necessary for viral infection/replication in mouse cell.

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.