Clinical development of the novel oncolytic coxsackievirus B3 targeting malignant tumors

2014 Fiscal Year Final Research Report

• Project/Area Number: 23240133
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Kyushu University
• Principal Investigator: TANI Kenzaburo 九州大学, 生体防御医学研究所, 教授 (00183864)
• Co-Investigator(Renkei-kenkyūsha): SHIMIZU Hiroyuki 国立感染症研究所, ウイルス第2部, 室長 (90270644)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 腫瘍溶解性ウイルス / コクサッキーウイルスB群3型 / miRNA / 顆粒球マクロファージ刺激因子 / ウイルス製剤製造 / 一般毒性試験

Outline of Final Research Achievements

Oncolytic viruses are characterized by self-replicating and tumor killing capacity, and have emerged as a promising treatment platform for cancer therapy. We previously carried out the screening of approximately 40 enterovirus strains and found that CVB3 possessed specific oncolytic activity against cell lines of human lung cancer, malignant pleural mesothelioma and breast cancer. In this study, two experiments were performed for the development of the novel oncolytic coxsackievirus B3 therapy. (1) To overcome CVB3-related organ toxicities, we constructed a novel recombinant CVB3-miRT by genetically incorporating two distinct normal tissue-specific miRNA target sequences into the CVB3 genome. We next constructed CVB3 inserting GM-CSF gene (CVB3-GM-CSF) to improve anti-tumor immunity. (2) For the purpose of producing CVB3 reagent under Good Manufacturing Practice (GMP), we developed mass production method using GMP grade reagents and instruments.

Free Research Field

血液腫瘍学