AFP and hepatocellular carcinoma: Consistent with these in vitro results, the oncolytic Ad, replicating under the control of the Ha2bm promoter (Ha2bm-d19), showed higher HCC-specific and potent antitumor activity than did the a2bm-d19-driven Ad in AFP-positive HCC orthotopic xenograft tumors; this is because HREs, upstream of the Ha2bm promoter, enhance viral replication and gene expression in the hypoxic tumor region40,51–53 (Figs 2C, 4E and 5C).