Potentiation of cancer immunotherapy using spatiotemporal regulation of heat shock protein-TLR ligand complex

利用热休克蛋白-TLR配体复合物的时空调节增强癌症免疫治疗

• 批准号: 23590427
• 负责人: MATSUZAKI Junichi
• 金额: $ 3.41万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590427/
• 关键词: がんペプチドワクチン; 熱ショック蛋白質; 自然免疫; 細胞障害性T細胞; クロスプレゼンテーション; 樹状細胞; 抗原ペプチド; 免疫賦活剤; Hsp90; Hsp72; TLR; 形質細胞様樹状細胞; CpG; LPS; Toll様受容体; 癌ワクチン

We have demonstrated that Hsp90 can act as an efficient inducer for crosspresentation of associated antigenic peptide via spatiotemporal regulation. We examined whether vaccination with Hsp90-antigen peptide complex and TLR ligand augmented the induction of cytotoxic T cell (CTL) response via crosspresentation. Interestingly, plasmacytoid dendritic cells (pDCs) secreted not only IFN-a but also Hsp72 in response to CpG-A administration. We found that the secreted Hsp72 formed complex with Hsp90-peptide complex, leading to the efficient crosspresentation and CTL induction against associated peptide. These data suggest that CpG-A is a good candidate as an immunoadjuvant for Hsp90-based cancer vaccine.

我们已经证明，HSP90可以通过时空调节来充当相关抗原肽的交叉侵蚀剂的有效诱导剂。我们检查了Hsp90-抗原肽复合物和TLR配体的疫苗接种是否通过交叉表达增强了细胞毒性T细胞（CTL）反应的诱导。有趣的是，浆细胞样树突状细胞（PDC）不仅分泌IFN-A，还分泌HSP72，以响应CPG-A给药。我们发现，分泌的HSP72与HSP90肽复合物形成复合物，从而导致对相关肽的有效交叉呈次介质和CTL诱导。这些数据表明，CPG-A是基于HSP90的癌症疫苗的免疫辅助剂的好候选者。

项目成果

Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population

• DOI: 10.1016/j.yexmp.2011.09.016
• 发表时间: 2012-02-01
• 期刊: EXPERIMENTAL AND MOLECULAR PATHOLOGY
• 影响因子: 3.6
• 作者: Mori, Takashi;Nishizawa, Satoshi;Sato, Noriyuki
• 通讯作者: Sato, Noriyuki

New paradigm for intrinsic function of heat shock proteins as endogenous ligands in inflammation and innate immunity.

• DOI: 10.2174/156652412803306710
• 发表时间: 2012-10
• 期刊: Current molecular medicine
• 影响因子: 2.5
• 作者: Y. Tamura;T. Torigoe;G. Kutomi;K. Hirata;N. Sato

熱ショック蛋白質HSPによる自己免疫疾患制御

热休克蛋白 HSP 控制自身免疫性疾病

• 作者: 奥寺康司;矢澤卓也;田尻道彦;下山田博明;北村均;田村保明
• 通讯作者: 田村保明

Cytotixic T lymphocytes efficiently recognize human colon cancer stem-like cells

细胞毒性T淋巴细胞有效识别人结肠癌干样细胞

• 发表时间: 2011
• 期刊: Am. J. Pathol
• 作者: Inoda;S.;Hirohashi;Y.;Torigoe;T.;Takahashi;A.;Morita;R.;Nakatsugawa;M.;Nishizawa;S.;Tamura;Y.;Tsuruma;T.;Terui;T.;Ishitani;K.;Hirata;K. and Sato;N.
• 通讯作者: N.

Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients

• DOI: 10.1111/j.1349-7006.2011.01918.x
• 发表时间: 2011-06-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Kameshima, Hidekazu;Tsuruma, Tetsuhiro;Hirata, Koichi
• 通讯作者: Hirata, Koichi