Development of peptide vaccine therapy targeting oral cancer stem cells with comprehensive HLA ligandome analysis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K17282
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: University of the Ryukyus (2019); Sapporo Medical University (2017-2018)
• Principal Investigator: Miyamoto Sho 琉球大学, 医学部附属病院, 助教 (80749565)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ペプチドワクチン / がん幹細胞 / 腫瘍免疫 / がん免疫

Outline of Final Research Achievements

Cancer stem cells (CSCs) explain the resistance to chemo/radiotherapies and cancer-initiating abilities of low numbers of cells in vivo. In order to target them through CTL recognition, we first isolated the CSC population from the cancer line, SW480, with an established side-population method. And screened the natural HLA-A24 ligandome by LC-MS/MS, resulting in identification of a CSC-specific natural antigenic peptide, IV9.
The IV9 specific CTLs were induced from PBMC stimulated by IV9 peptide. IV9 specific CTL recognized CSCs but not non-CSCs. And in immunodeficient mice, intravenous injection of the IV9 specific CTL successfully prevented growth of the original SW480 cells. As the cancer cells implanted in these mice contained very few CSCs, the elimination of a CSC subset could be the condition necessary and sufficient to control tumor formation in vivo. These results suggest that CTL-based immunotherapies against colorectal CSCs might be useful for preventing relapses.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

がん解細胞を標的とした、新規ペプチドワクチンの開発に成功した。また本研究を通し、がん幹細胞成分を排除することが、腫瘍形成を制御するのに必要かつ十分な条件であることを証明している。このことは、CTL免疫療法の治療・予防戦略において、がん幹細胞を標的とすることの有効性を示唆する結果となっており、今後のあらゆるがんの再発予防法の開発・研究を行うにあたり、指標となる重要な結果が得られた。