Development of NK Cell expansion by a novel membrane-bound chimeric cytokine

• Project/Area Number: 18K07259
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Niigata University
• Principal Investigator: Imamura Masaru 新潟大学, 医歯学総合病院, 講師 (80464006)
• Co-Investigator(Kenkyū-buntansha): 今井 千速 新潟大学, 医歯学系, 准教授 (90419284)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膜結合型サイトカイン / 細胞療法 / NK細胞 / NK細胞療法 / 腫瘍免疫 / 膜結合型キメラサイトカイン / NK細胞増幅 / 免疫細胞療法

Outline of Final Research Achievements

The purpose of this study is to develop membrane-bound chimeric cytokines to increase NK cells without systemic administration of cytokines that may cause side effects and to realize safe and effective NK cell therapy. First, we generated the construct of hybrid membrane-bound interleukins 15 and 21. Next, we transduced the construct into a tumor cell line, K562 necessary for the expansion of NK cells, and the efficiency of transduction was as high as 85.5%. When we examined the expansion of NK cells transfected with the construct, we found that the expansion was 27-fold after 7 days, but not as expected.

Academic Significance and Societal Importance of the Research Achievements

膜結合型サイトカインはサイトカイン分泌を伴わないため全身投与より安全と考えられる。サイトカインの種類及び構造の最適化によりNK細胞を効率的に増やすことができ、安全で効果的な新規NK細胞療法の実現が可能になると考えられる。今回新しく開発したIL-15とIL-21のハイブリッド膜結合型サイトカインはNK細胞を十分に増やす効果は得られず、新たな工夫が必要と考えられた。