Development of 3rd generation anti-CD19 chimeric receptor for primary natural killer cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 25860847
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Niigata University
• Principal Investigator: Yoshida Sakiko 新潟大学, 医歯学総合研究科, 客員研究員 (30535183)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 遺伝子改変NK細胞療法 / 小児再発・難治性白血病

Outline of Final Research Achievements

Development of new targeted therapy for primary refractory or relapse leukemia in childhood is needed to overcome cellular resistance to current chemotherapy. We previously reported genetic modification of primary human NK cells by enforced expression of anti-CD19 chimeric receptors linked to CD3 zeta; (1st generation chimeric receptor) and CD3 zeta plus 4-1BB signaling molecules (2nd generation) could　markedly enhanced cytotoxicity against leukemic cells. To further enhance cellular functions, we developed the 3rd generation chimeric receptor with triple signaling molecules. The novel construct of the 3rd generation was successfully transduced with primary NK cells. Surface expression of the chimeric receptors was relatively low compared to 1st and 2nd generation, however, the function of cytotoxicity was confirmed as same level as previous generations. We plan to assess the potential for further improvement of surface expression and function of the 3rd chimeric receptor.

Free Research Field

医歯学