Interferon-expressing oncolytic adenovirus + chemoradiation inhibited pancreatic cancer growth in a hamster model

Cancer Sci. 2023 Sep;114(9):3759-3769. doi: 10.1111/cas.15903. Epub 2023 Jul 13.


Past clinical trials of adjuvant therapy combined with interferon (IFN) alpha, fluorouracil, cisplatin, and radiation improved the 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC). However, these trials also revealed the disadvantages of the systemic toxicity of IFN and insufficient delivery of IFN. To improve efficacy and tolerability, we have developed an oncolytic adenovirus-expressing IFN (IFN-OAd). Here, we evaluated IFN-OAd in combination with chemotherapy (gemcitabine + nab-paclitaxel) + radiation. Combination index (CI) analysis showed that IFN-OAd + chemotherapy + radiation was synergistic (CI <1). Notably, IFN-OAd + chemotherapy + radiation remarkably suppressed tumor growth and induced a higher number of tumor-infiltrating lymphocytes without severe side toxic effects in an immunocompetent and adenovirus replication-permissive hamster PDAC model. This is the first study to report that gemcitabine + nab-paclitaxel, the current first-line chemotherapy for PDAC, did not hamper virus replication in a replication-permissive immunocompetent model. IFN-OAd has the potential to overcome the barriers to clinical application of IFN-based therapy through its tumor-specific expression of IFN, induction of antitumor immunity, and sensitization with chemoradiation. Combining IFN-OAd with gemcitabine + nab-paclitaxel + radiation might be an effective and clinically beneficial treatment for PDAC patients.

Keywords: interferon alpha; nab-PTX; oncolytic adenovirus; oncolytic virus; pancreatic cancer.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae Infections*
  • Albumins
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Cell Line, Tumor
  • Cricetinae
  • Humans
  • Interferon-alpha
  • Paclitaxel
  • Pancreatic Neoplasms* / metabolism
  • Virus Replication


  • Interferon-alpha
  • Paclitaxel
  • Albumins