Preclinical study of tumor-specific p53 gene therapy against refractory pancreatic cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10596
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Okayama University
• Principal Investigator: TAZAWA HIROSHI 岡山大学, 大学病院, 准教授 (90415513)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 膵臓癌 / p53 / KRAS / 腫瘍融解 / アデノウイルス / オートファジー / 免疫原性細胞死

Outline of Final Research Achievements

Pancreatic ductal adenocarcinoma (PDAC) frequently shows invasion and metastasis, leading to treatment resistance and poor prognosis. The development of novel antitumor strategy for PDAC is an urgent issue. Here, we show that a tumor-specific replication-competent oncolytic adenovirus expressing tumor suppressor p53, OBP-702, inhibits the migration and invasion abilities and tumor growth and induces the immunogenic cell death in human PDAC cells. In the future, the clinical application of a multiplidisciplinary therapy with OBP-702 is important.

Free Research Field

分子腫瘍学、遺伝子治療学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、高率にKRAS癌遺伝子やp53癌抑制遺伝子の異常を伴う膵臓癌に対して癌特異的増殖型ウイルスを用いたp53遺伝子治療がp53シグナルの活性化とKRAS-ERKシグナルの抑制を介して抗腫瘍効果を発揮する新たな治療戦略となる可能性を示唆している。予後不良な膵臓癌は有効な治療法の確立に未だ至っておらず、新規治療法の開発研究は膵臓癌患者の生命予後の改善につながるため社会的意義は大きい。