Application of anti-cancer effector cells that exert adjuvant effects for lung cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861253
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory surgery
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: ZHANG Rong 愛知県がんセンター(研究所), 腫瘍免疫学部, リサーチレジデント (00643719)
• Research Collaborator: KUZUSHIMA Kiyotaka 愛知県がんセンター研究所, 部長 (30311442) ; UEMURA Yasushi 国立がんセンター, ユニット長 (40364781)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 肺がん / 免疫 / 遺伝子療法 / 細胞療法

Outline of Final Research Achievements

Adoptive immunotherapy using TCR gene-modified T cells is an attractive strategy for targeting cancer. However, naturally occurring TCRs are of lower affinity, a fact that limits the ability of natural TCRs to recognize the low antigen-HLA levels typically expressed on tumor cells. To address this issue, we used invariant NKT (iNKT) cells, a unique subset of T cells that recognize α-GalCer presented by CD1d, as a cellular adjuvant. We found that soluble factors from iNKT cell/α-GalCer-dendritic cell (DC) interaction enhanced the HLA-I expression on cancer cells and upregulated both perforin and granzyme B in TCR gene-modified T cells, in turn enhancing the potency of cellular immunity. Furthermore, in vivo transfer of TCR gene-modified T cells in combination with iNKT/α-GalCer-DC inhibited the tumor growth and significantly prolonged the survival in xenograft model. Thus, the additional transfer of iNKT/α-GalCer-DC may improve the efficacy of TCR gene-modified T cells.

Free Research Field

腫瘍免疫学