Study of nano particle cancer vaccines targeting for Dendritic cells.

• Project/Area Number: 17K01371
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Tokyo Medical University
• Principal Investigator: Yanase Noriko 東京医科大学, 医学部, 兼任助教 (10210303)
• Co-Investigator(Kenkyū-buntansha): 秦 喜久美 東京医科大学, 医学部, 講師 (30287156) ; 豊田 博子 東京医科大学, 医学部, 助手 (80468660)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: がん / 免疫 / ワクチン / ナノ粒子 / がんワクチン / ガンワクチン / 免疫学 / ナノバイオ / 癌

Outline of Final Research Achievements

Humanized mouse was created by transferred human hematopoietic stem cells into the severe complex immunodeficiency mice, NOD-Prkdcscid-IL2R null (NSG) -HLA-A * 0201.A humanized mouse in which 80% or more of human lymphocytes (hCD45 positive cells) in peripheral blood 　 could be prepared and used in the vaccine experiments.These humanized mice were vaccinated with anti-DEC205 antibody-binding HER2 peptide-CpG ODN-encapsulating micelles and then the HER2-positive breast cancer cell line JIMT-1-HLA-A * 0201 was transferred.　On day 14 of transplantation, the control group had a tumor size of 200 mm3, while the anti-DEC205 antibody-binding HER2 peptide-CpG ODN-encapsulating micelle-treated group had a tumor size half that.In these experimental groups, tumor growth was suppressed even on the 21st day of transplantation.

Academic Significance and Societal Importance of the Research Achievements

以上の結果からがんワクチンとして樹状細胞特異抗原に対する抗体を結合したHER2ペプチド-CpG ODN内包ミセルは樹状細胞を有効に惹起し、抗腫瘍活性がヒト化マウスで働いていると考えられ、ヒト乳がん治療での有効性が期待できることが明らかになった。
しかしながら、ヒトでの実用化あたっては臨床を含めた更なる実証が必要と考えられる。