State-of-the-art in oncolytic virotherapy using adenoviruses other than the commonly applied adenovirus type 5

In most clinical trials, oncolytic viruses (OAds) based on human adenovirus type 5 (HAdV-C5) were explored, and only rarely a complete switch to another adenovirus type was evaluated. This review highlights the broader diversity of human adenoviruses and discusses advances in engineering non-HAdV-C5 OAds. We will discuss ongoing research to refine adenoviral constructs derived from alternative adenovirus species, including chimeric viruses, to optimize viral delivery and enhance antitumor immune responses. We summarize translational and clinical studies using these alternative OAds, emphasizing their therapeutic promise despite remaining challenges. Unlocking the full potential of diverse OAds could significantly expand cancer treatment options.