A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency

The absence or the presence of low levels of the Coxsackievirus and adenovi rus receptor (CAR) on several tumor types might limit the efficacy of recen tly proposed tumor-specific or conditionally replicative adenoviruses (CRAd s), To address this issue, we used a genetic modification of the fiber knob in the context of an E1A-defective CRAd to allow CAR-independent target ce ll infection as a means to enhance oncolytic potency, Such infectivity-enha nced CRAd showed higher replication, more efficient infection, and lysis of tumor cells in vitro. Of note, the improved antitumor effect of the fiber- modified CRAd could be demonstrated in vivo. We conclude that the combinati on of genomic modification to achieve tumor-selective replication and capsi d modification to enhance infectivity yields more potent oncolytic adenovir uses for use in cancer treatment.