Gene delivery from the E3 region of replicating human adenovirus: evaluation of the E3B region

Successful therapies for cancer need to deal with the complexity associated with the human tumor. Studies of tumor and viral biology have progressed t o a point where replicating viruses are now being engineered as potential t reatments for human cancers. The complex nature of human cancers dictates t hat successful treatments will require combination therapies. To this end, we have focused on developing the gene delivery capacity of the replicating adenovirus, using the non-essential E3 region transcription unit as a targ et site for therapeutic transgene Insertions. Utilizing the endogenous expr ession machinery of the E3 region (promoter, splicing, polyA) we show that a therapeutic transgene, TNF, is efficiently expressed from the E3B region and with exclusive late gene expression kinetics. Potential clinical applic ations are discussed.