Enhanced hyaluronidase and tumor neoepitope expression by oncolytic adenoviruses

Abstract

The oncolytic viruses (OVs) preferentially infect tumor and selectively replicate in cancer cells without harming normal tissues. OVs have been tested in clinical trials as monotherapy or combined with chemotherapy, radiotherapy, and immunotherapy. Nonetheless, the intratumoral spreading and the immune response hamper the treatment efficacy. In this thesis, these two challenges have been addressed in three separate chapters. First, VCN-01, a hyaluronidase-expressing oncolytic adenovirus, was tested in a clinical trial in pancreatic cancer patients. We assessed the immune response triggered by VCN-01 as monotherapy or in combination with chemotherapy. We reported an early anti-viral immune response induction of IL-6, IL-10, IFNγ, IDO1, IP-10, and sLAG-3 in serum, independently of chemotherapy. We found a correlation between treatment toxicity and the IL-6 and IL-10. Furthermore, the triggered anti-viral immune response such as IFNγ, sLAG-3, and neutralizing antibodies anti-Ad5 was associated with better antitumor activity in patients. The neoepitope vaccines have been tested in patients with limited clinical responses. We hypothesized that an oncolytic adenovirus (OAd) encoding for stroma.