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

2014 Fiscal Year Final Research Report

• 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
• Keywords: cancer stem cell / IFN-alpha / phage display library

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.

Free Research Field

タンパク質工学