Development of in vivo cytotoxicity assay system using humanized mice increasing human natural killer cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25871075
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science; Tumor therapeutics
• Research Institution: Central Institute for Experimental Animals
• Principal Investigator: Katano Ikumi 公益財団法人実験動物中央研究所, その他部局等, 研究員 (90442558)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ヒト化マウス / NK細胞 / ヒト免疫 / ｈIL-2 / hIL-15

Outline of Final Research Achievements

We previously reported that human NK cells are predominately developed in NOG-hIL-2 Tg mice after human hematopoietic stem cell (HSC) transplantation. In this study, we assessed in vivo antibody-dependent-cellular-cytotoxicity (ADCC) activity using human HSC-transferred NOG-hIL-2 Tg mice engrafted with CCR4 expressing Hodgkin’s lymphoma cell line L428. After treatment with an anti-CCR4 antibody, tumor growth was slightly suppressed in NOG-hIL-2 Tg mice. To improve the function of NK cells, we generated a NOG-hIL-15 Tg mouse. Although human mature NK cells were dominantly differentiated in NOG-hIL-15 Tg mice, they immediately died within 8 weeks after HSC transplantation. In contrast, human peripheral blood-derived mature NK cells succeeded to be maintained over 3 months after transplantation without death. Moreover, these NK cells showed in vivo cytotoxic activity against engrafted K562 cells. Therefore, NOG-hIL-15 Tg mice are useful tools for investigation of in vivo NK cytotoxicity.

Free Research Field

免疫学、実験動物学