Reprogramming and re-differentiation of invariant NKT cells for pancreatic cancer immunotherapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462078
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: National Cancer Center Japan
• Principal Investigator: UEMURA Yasushi 国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (40364781)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 外科 / 膵臓 / がん / 免疫

Outline of Final Research Achievements

Vα24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. Reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-2/IL-15-based optimized cytokine combination. The re-differentiated iNKT cells showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of cytotoxic T lymphocytes, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines.
The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against pancreatic cancer.

Free Research Field

腫瘍免疫学