Studies towards development of more effective NK cell therapy: Finding genetic determinants for selection of best NK cell donors and a novel method for transfer of chimeric antigen receptor protein

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Niigata University
• Principal Investigator: Imai Chihaya 新潟大学, 医歯学系, 准教授 (90419284)
• Co-Investigator(Renkei-kenkyūsha): SAKIKO YOSHIDA 新潟大学, 医歯学総合研究科, 客員研究員 (30535183)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: NK細胞 / 白血病 / がん / KIR / NKG2D / trogocytosis / 造血幹細胞移植

Outline of Final Research Achievements

In this study towards development of more effective natural killer (NK) cell therapy against cancer and leukemia, we investigated on the genetic determinants that can predict individuals’ NK cell functions. In healthy adults, we observed significant association of NKG2D haplotypes with NK cell functions. We also observed association of KIR haplotypes with in-vitro cytokine/chemokine production. In addition, we found that donor KIR haplotypes significantly affected the clinical outcomes such as acute GVHD after allogeneic hematopoietic stem cell transplantations. In addition to the abovementioned studies, we investigated on a novel method to transfer chimeric antigen receptor into human primary NK cells by using trogocytosis phenomenon to confer them capability to kill malignant cells in an antigen-specific manner. Expression by using trogocytosis was possible, but expression levels were not enough for clinical translation and will require further modification and improvement.

Free Research Field

小児血液学