Local oncolytic adenovirotherapy inducing the direct abscopal effect via exosome

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17617
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Okayama University
• Principal Investigator: Kakiuchi Yoshihiko 岡山大学, 大学病院, 医員 (70868356)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 細胞外小胞 / ウイルス療法 / アブスコパル効果 / アデノウイルス / ドラッグデリバリーシステム

Outline of Final Research Achievements

Local administration of a telomerase specific oncolytic adenovirus, OBP-301, was sometimes occurred shrinkage of metastatic lymph nodes as well as directly-administered primary tumors. We used a bilateral subcutaneous tumor model in immunodeficient mice, and in immunocompetent mice. Local administration of OBP-301 on one side delivered their-derived substances to opposite side and produced potent therapeutic effects on untreated tumor as well, suggesting that immune modulation by viruses were involved in this abscopal effect. Interestingly, in the presence of an exosome production inhibitor, these phenomenon was not observed. These results suggested that involvement of exosome encapsulating adenoviruses were demonstrated. We conclude that OBP-301 local administration has remarkable and intriguing potential to cause the abscopal effect through exosome-mediated systemic delivery of OBP-301 in addition to immune activation.

Free Research Field

がん治療

Academic Significance and Societal Importance of the Research Achievements

本研究では、OBP-301のエクソソームを介した全身性の直接的な抗腫瘍効果メカニズムの解明した。OBP-301の投与は腫瘍への局所投与に限定されるため、遠隔転移部への治療効果は期待できないと考えられていたが、本研究での結果、エクソソームを介した直接的な全身性の治療効果は全く新しい治療メカニズムであり、本研究の成果はOBP-301のみならずウイルス療法全体の魅力をさらに高め、実臨床への応用へと役立つ研究結果であると言える。