A novel peptide vaccine therapy using in vivo antigen delivery to XCR1+DCs
| Project/Area Number |
16K10608
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山上 裕機 和歌山県立医科大学, 医学部, 教授 (20191190)
松田 健司 和歌山県立医科大学, 医学部, 講師 (30398458)
尾島 敏康 和歌山県立医科大学, 医学部, 講師 (60448785)
宮澤 基樹 和歌山県立医科大学, 医学部, 助教 (90549734)
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| Research Collaborator |
KAISHO Tsuneyasu
HEMMNI Hiroaki
MIZUMOTO Yuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腫瘍免疫 / がんワクチン / ペプチド / 樹状細胞 / XCR1 / XCL1 / ペプチドワクチン / ドラッグデリバリー / 膵臓外科学 / 腫瘍免疫学 |
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| Outline of Final Research Achievements |
We aimed to generate selectively delivering antigen peptides to an XC chemokine receptor 1-expressing dendritic cell subset(XCR1+DC) that is notable for its exceptional ability to generate CTL response. To do that, we designed a vaccine(mXCL1-OVA peptide vaccine)that consisted of a murine XCR1 ligand(XCL1)and an ovalbumin(OVA)-derived MHC class I-restricted antigen. When co-injected with polyinosinic-polycytidylic acid(poly[I: C]), mXCL1-OVA peptide vaccine induced much greater amount of antigen-specific cytotoxic T cells(CTL) than either OVA protein plus poly(I: C)or OVA peptide plus poly(I: C). Furthermore, mXCL1-OVA peptide vaccine plus poly(I: C)showed more prominent antitumor effects against OVA-expressing melanoma(B16-OVA)than other vaccines with regard to growth inhibition. Thus, our results suggest that chemokine-directed antigen delivery to DC subsets with high CTL-inducing ability is a promising method for generating effective antitumor immunity.
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| Academic Significance and Societal Importance of the Research Achievements |
抗原提示細胞は不均一な細胞集団であり、免疫応答活性化するばかりでなく抑制するサブセットも含まれる。すなわち、がん抗原由来エピトープペプチドをワクチンとして直接投与する従来の方法では抗原がすべての抗原提示細胞に送達され、抗腫瘍効果が制限されていた可能性が考えられるた。最近、ケモカイン受容体XCR1を発現する樹状細胞サブセットXCR1+DCが強力なCTL誘導活性を示すことが明らかになったことに着目し、本研究ではこの樹状細胞サブセットに抗原を選択的に送達し、効率よく抗原特異的なCTLを誘導することで強力な抗腫瘍効果が誘導される新しいタイプのがんペプチドワクチン療法を開発、確立できることが示唆された。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] In Vivo Antigen Delivery to Dendritic Cells-A Novel Peptide Vaccine for Cancer Therapy2018
Author(s)
yuki mizumoto, masahiro katsuda, motoki miyazawa, yuji kitahata, atsushi miyamoto, mikihito nakamori, toshiyasu ojima, kenji matsuda, h hemmi, koji tamada, tsuneyasu kaisho, hiroki yamaue
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Journal Title
gan to kagaku ryouho
Volume: 45(10)
Pages: 1469-1471
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[Presentation] がんワクチン創薬を目指して2017
Author(s)
Masahiro Katsuda, Motoki Miyazawa, Yuji Kitahata, Yuki Mizumoto, Ojima, Atsushi Miyamoto and Hiroki Yamaue
Organizer
第6回 日本免疫・細胞治療学会 学術総会
Related Report
Invited
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