Development of mutant IFN-alpha as a drug against the chemo-resistance of cancer stem cells

Research Project

Project/Area Number	26670061
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Drug development chemistry
Research Institution	独立行政法人医薬基盤研究所
Principal Investigator	TSUNODA Shin-ichi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (90357533)
Project Period (FY)	2014-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000) Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords	cancer stem cell / IFN-alpha / phage display library / 蛋白質 / バイオ医薬 / がん
Outline of Final Research Achievements	For advancement of cancer chemotherapy, development of a novel method to attack the cancer stem cells (CSCs) which are resistant to anticancer drugs is needed. Resistance to chemotherapy of CSCs is depends on their dormant state of cell cycle. Recent study revealed that such a dormant state of cell cycle of stem cells was caused by inhibition of IFN-α signal transduction. This suggests the possibility that potent IFN-α signal may remove the chemo-resistance of CSCs. In order to investigate the above hypothesis, we tried to produce IFN-α mutants of high bioactivity and cell cycling activity for stimulate the cell cycle of CSCs. To this end, we performed a screening of IFN-α8 mutants by our original technology creating functional cytokine mutants using phage display library system. By using our technology, several potential IFN-α8 mutants have been successfully isolated. These IFN-α mutants could be a promising adjuvant for cancer chemotherapy.