Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy

To date, diverse combination therapies with immune checkpoint inhibitors (ICIs), particularly oncolytic virotherapy, have demonstrated enhanced therapeutic outcomes in cancer treatment. However, high pre-existing immunity against the widely used adenovirus human serotype 5 (AdHu5) limits its extensive clinical application. In this study, we constructed an innovative oncolytic virus (OV) based on a chimpanzee adenoviral vector with low seropositivity in the human population, named AdC68-spE1A-aPD-1, which endows the parental OV (AdC68-spE1A-DE3) with the ability to express full-length anti-human programmed cell death-1 monoclonal antibody (aPD-1). In vitro studies indicated that the AdC68-spE1AaPD-1 retained parental oncolytic capacity, and aPD-1 was efficiently secreted from the infected tumor cells and bound moral treatment with AdC68-spE1A-aPD-1 resulted in significant tumor suppression, prolonged overall survival, and enhanced systemic antitumor memory response in an hPD-1 knockin mouse tumor model. This strategy outperformed the unarmed OV and was comparable with combination therapy with intratumoral injection of AdC68-spE1A-DE3 and systemic administration of commercial aPD-1. In summary, AdC68-spE1A-aPD-1 is a cost-effective approach with potential clinical applications.