Human species C adenovirus serotype 5 (Ad5) is the archetype oncolytic adenovirus and has been used in the vast majority of preclinical and clinical tests. While Ad5 can be robust， species C Ad6 has lower seroprevalence， side effects， and appears to be more potent as a systemic therapy against a number of tumors than Ad5. Historically， there have only been four species C human adenoviruses: serotypes 1， 2， 5， and 6. More recently a new species C adenovirus， Ad57， was identified. Ad57 is most similar to Ad6 with virtually all variation in their capsid proteins occurring in the hypervariable regions (HVRs) of their hexon proteins. Most adenovirus neutralizing antibodies target the HVRs on adenoviruses. This led us to replace the hexon HVRs in Ad6 with those from Ad57 to create a new virus called Ad657 and explore this novel species C platform's utility as an oncolytic virus.