Generation of TRAIL positive NK cells from hematopoietic stem cells / iPS cells in vitro for anti-HCC immunotherapy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591880
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: TANAKA Yuka 広島大学, 医歯薬保健学研究院(医), 准教授 (90432666)
• Co-Investigator(Kenkyū-buntansha): OHDAN Hideki 広島大学, 医歯薬保健学研究院(医), 教授 (10363061) ; ISHIYAMA Kohei 広島大学, 大学病院, 病院助教 (50437589)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: NK細胞 / 肝臓癌 / 細胞免疫療法

Outline of Final Research Achievements

We have previously reported that IL-2-stimulated CD56+ cells derived from the liver exert vigorous cytotoxicity against HCC. To differentiate NK cells, we incubated bone marrow-derived CD34+ hematopoietic progenitor cells in 5% serum-supplemented X-VIVO-15 medium containing SCF, Flt-3, IL-7, and IL-15. These NK cells expressed NKp46, a specific receptor of NK cells, and were phenotypically similar to resident NK cells, i.e. they expressed TRAIL, NKG2D, and CD226. The propagated NK cells produced IFN-γ. The propagated NK cells exhibited vigorous cytotoxicity against HCC cell lines by using 51Cr release assay. We have also developed a method to differentiate CD34+ hematopoietic progenitor cells from fibroblast-derived iPS cells. The use of NK cells for immunotherapy relies on the availability of large numbers of purified NK cells with optimal anti-HCC activities. This adaptive immunotherapy with these cells may be a promising modality to prevent the recurrence of HCC after hepatectomy.

Free Research Field

移植免疫学