Efficient antitumor effects of a novel oncolytic adenovirus fully composed of species B adenovirus serotype 35
Autor: | Kosuke Takayama, Ryosuke Ono, Fuminori Sakurai, Hiroyuki Mizuguchi |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Oncolytic adenovirus Cancer Research Lysis viruses lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Pharmacology (medical) Neutralizing antibody Receptor CD46 oncolytic virus biology neutralizing antibody lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oncolytic virus CAR adenovirus serotype 35 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Molecular Medicine Original Article Antibody |
Zdroj: | Molecular Therapy: Oncolytics, Vol 20, Iss, Pp 399-409 (2021) Molecular Therapy Oncolytics |
ISSN: | 2372-7705 |
Popis: | Oncolytic adenoviruses (OAds) are among the most promising oncolytic viruses. Almost all oncolytic adenoviruses are composed of human adenovirus serotype 5 (Ad5) (OAd5). However, expression of the primary infection receptor for Ad5, coxsackievirus-adenovirus receptor (CAR), often declines on malignant tumor cells, resulting in inefficient infection in CAR-negative tumor cells. In addition, at least 80% of adults have neutralizing antibodies against Ad5. In this study, we developed a novel OAd fully composed of OAd35. OAd35 recognizes CD46, which is ubiquitously expressed on almost all human cells and is often upregulated on malignant tumor cells, as an infection receptor. Moreover, 20% or fewer adults have neutralizing antibodies against Ad35. OAd35 mediated efficient cell lysis activities at levels similar to OAd5 in CAR-positive tumor cells, while OAd35 showed higher levels of cell lysis activities than OAd5 in CAR-negative tumor cells. Anti-Ad5 serum significantly inhibited in vitro tumor cell lysis activities of OAd5, whereas OAd35 exhibited comparable levels of in vitro tumor cell lysis activities in the presence of anti-Ad5 and naive serum. OAd35 significantly suppressed growth of the subcutaneous CAR-positive and CAR-negative tumors following intratumoral administration. These results indicated that OAd35 is a promising alternative oncolytic virus for OAd5. Graphical Abstract A conventional oncolytic adenovirus (OAd) based on adenovirus serotype 5 (Ad5) is a promising anticancer agent. However, more than 80% of adults have neutralizing anti-Ad5 antibodies. OAd serotype 5 inefficiently infects coxsackievirus-adenovirus receptor-negative tumors. In order to overcome these drawbacks, we developed a novel OAd composed of Ad35. |
Databáze: | OpenAIRE |
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