Cellular and Molecular analyses of cancer-associated antigen-specific cytotoxic T cells by multidimensional methods and development of novel cancer immunotherapy
| Project/Area Number |
19K07729
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | がん免疫療法 / がんワクチン / WT1 / T細胞受容体 / 膵臓がん / 細胞傷害性T細胞 / TCRレパトア / single cell RNAseq / がんワクチン療法 |
|---|
| Outline of Research at the Start |
難治ながんの1つである膵臓がんに対する新たな治療戦略として、我々はWT1がんワクチン療法と抗がん剤治療との併用療法の有効性を臨床試験を通して報告したが、全例に顕著な効果は一部の症例のみであった。今回の研究では、本治療法の臨床効果の中心を担う免疫担当細胞であるWT1抗原特異的細胞傷害性T細胞（CTL)の機能的・質的な解析を行い、効果が顕著に認められた症例でのWT1特異的CTLの特性が、効果不十分な症例のものに比較してどう異なるのか？、特にどのようなCTLがメモリーT細胞に分化し、どのように長期維持され、臨床効果につながるのか？という疑問を解明し、本治療法の更なる効果改善に寄与する研究を行う。
|
| Outline of Final Research Achievements |
WT1 is a promising cancer-associated antigen. We, here, evaluated the qualitative and functional changes in WT1-specific cytotoxic T cells, WT1-CTLs, induced during the combination therapy with cytotoxic drug and WT1 cancer vaccine for advanced pancreatic cancer patients.
It was essential for long-term clinical efficacy that WT1-CTLs, induced after treatment, obtained a memory function to maintain their antitumor immunity. Further, we found that some TCR clones of WT1-CTLs were shared among patients who had exhibited clinical efficacy. We will link these TCRs to the future development of new cancer immunotherapies.
|
| Academic Significance and Societal Importance of the Research Achievements |
今回の成果はWT1を標的としたがん免疫療法（細胞療法）の開発につながる。個々の患者のがん特異的なネオ抗原に対するT細胞受容体の同定が個別化医療となることに対して、汎腫瘍抗原であるWT1に特異的なキラーT細胞が持つT細胞受容体を同定することは、膵癌のみならずWT1を発現するがんを患った患者に応用が可能であることを意味する。免疫チェックポイント阻害薬の効果が乏しいとされる、いわゆる“cold”ながんに対する治療戦略を将来発展させうる１つの成果である。
|
Report
(4 results)
Research Products
(7 results)
-
[Journal Article] Cellular and Humoral Immune Responses Induced by an HLA Class I-restricted Peptide Cancer Vaccine Targeting WT1 Are Associated With Favorable Clinical Outcomes in Advanced Ovarian Cancer.2022
Author(s)
Nishida S, Morimoto S, Oji Y, Morita S, Shirakata T, Enomoto T, Tsuboi A, Ueda Y, Yoshino K, Shouq A, Kanegae M, Ohno S, Fujiki F, Nakajima H, Nakae Y, Nakata J, Hosen N, Kumanogoh A, Oka Y, Kimura T, Sugiyama H.
-
Journal Title
J Immunother.
Volume: 45
Issue: 1
Pages: 55-66
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] WT1 epitope-specific IgG and IgM antibodies for immune-monitoring in patients with advanced sarcoma treated with a WT1 peptide cancer vaccine.2022
Author(s)
Alzaaqi S, Naka N, Hamada K, Hosen N, Kanegae M, Outani H, Adachi M, Imanishi R, Morii E, Iwai M, Nakata J, Fujiki F, Morimoto S, Nakajima H, Nishida S, Tsuboi A, Oka Y, Sugiyama H, Oji Y.
-
Journal Title
Oncol Lett.
Volume: -
Issue: 2
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Identification of two distinct populations of WT1-specific cytotoxic T lymphocytes in co-vaccination of WT1 killer and helper peptides.2021
Author(s)
Fujiki F, Tsuboi A, Morimoto S, Hashimoto N, Inatome M, Nakajima H, Nakata J, Nishida S, Hasegawa K, Hosen N, Oka Y, Oji Y, Sogo S, Sugiyama H.
-
Journal Title
Cancer Immunol Immunother.
Volume: 70
Issue: 1
Pages: 253-263
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Immune adjuvant therapy using Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) in advanced malignancies: A phase 1 study of safety and immunogenicity assessments.2019
Author(s)
Nishida S, Tsuboi A, Tanemura A, Ito T, Nakajima H, Shirakata T, Morimoto S, Fujiki F, Hosen N, Oji Y, Kumanogoh A, Kawase I, Oka Y, Azuma I, Morita S, Sugiyama H.
-
Journal Title
Medicine (Baltimore)
Volume: 98
Issue: 33
Pages: e16771-e16771
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Presentation] 進行卵巣癌に対するWT1を標的とした癌ワクチンに関する臨床研究(Clinical Study of the Cancer Vaccine targeting WT1 for Advanced Ovarian Cancer)2019
Author(s)
西田 純幸, 白方 俊章, 森本 創世子, 榎本 隆之, 吉野 潔, 冨松 拓治, 藤木 文博, 尾路 祐介, 上田 豊, 坪井 昭博, 森田 智視, 岡 芳弘, 熊ノ郷 淳, 木村 正, 杉山 治夫
Organizer
日本がん免疫学会総会
Related Report
-
[Presentation] 進行肺癌に対するCpG ODN(K3)皮下注射による自然免疫の活性化(Activation of innate immunity in patients with advanced lung cancer following subcutaneous injection of CpG ODN(K3))2019
Author(s)
大塚 倫之, 西田 純幸, 濱口 眞成, 柴原 理志, 白山 敬之, 川合 祥子, 木村 恵子, 平田 陽彦, 木田 博, 石井 健, 熊ノ郷 淳
Organizer
日本がん免疫学会総会
Related Report
