C5 and neoplasm: Our findings therefore highlight that re-targeted HAdV-D10-based vectors may offer significant potential over HAdV-C5-based virotherapies, combining reduced off-target interactions with native receptors, providing a platform to engineer tropism toward high-affinity, “on-target” tumor-associated receptors and a capacity to circumvent pre-existing anti-HAdV-C5 immunity in the population.