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Interferon-expressing oncolytic adenovirus + chemoradiation inhibited pancreatic cancer growth in a hamster model.
Shinoda, Shuhei; Sharma, Nikita S; Nakamura, Naohiko; Inoko, Kazuho; Sato-Dahlman, Mizuho; Murugan, Paari; Davydova, Julia; Yamamoto, Masato.
Affiliation
  • Shinoda S; Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
  • Sharma NS; Department of Gastroenterology and Hepatology, Yamaguchi University Graduate school of Medicine, Yamaguchi, Japan.
  • Nakamura N; Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
  • Inoko K; Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
  • Sato-Dahlman M; Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
  • Murugan P; Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
  • Davydova J; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
  • Yamamoto M; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Cancer Sci ; 114(9): 3759-3769, 2023 Sep.
Article in En | MEDLINE | ID: mdl-37439437
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Adenoviridae Infections / Carcinoma, Pancreatic Ductal Limits: Animals / Humans Language: En Journal: Cancer Sci Year: 2023 Document type: Article Affiliation country: United States Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Adenoviridae Infections / Carcinoma, Pancreatic Ductal Limits: Animals / Humans Language: En Journal: Cancer Sci Year: 2023 Document type: Article Affiliation country: United States Country of publication: United kingdom