Development of effective immunotherapy by combining interventions on key points in the anti-tumor immune network

结合抗肿瘤免疫网络关键点的干预开发有效的免疫疗法

• 批准号: 23240128
• 负责人: KAWAKAMI Yutaka
• 金额: $ 31.37万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23240128/
• 关键词: がん免疫療法; 腫瘍抗原; 樹状細胞; T細胞; 免疫抑制; 免疫チェックポイント阻害; 免疫抑制制御; エフェクター細胞; 生体内腫瘍破壊法

In this sturdy, we have attempted to develop effective cancer immunotherapy by combining immune-regulating interventions on multiple important points in the cancer related positive and negative immune responses. We have developed and evaluated the following interventions; 1) interventions to induce immunogenic cancer cell death, 2) cancer antigens expressed in cancer stem cells which are resistant to chemotherapy, 3) interventions to stimulate antigen presenting dendritic cells for anti-cancer T-cell activation, 4) interventions to activate anti-cancer T-cells, 5) interventions to reverse cancer-induced immunosuppression. Using mouse tumor models, we have evaluated cancer immunotherapies in which the above interventions are appropriately combined, particularly with immune-checkpoint blockade therapies. These results may lead to development of more effective cancer immunotherapies through evaluation in the future clinical trials.

在这一过程中，我们尝试通过对癌症相关的阳性和阴性免疫反应中的多个重要点进行免疫调节干预来开发有效的癌症免疫疗法。我们制定并评估了以下干预措施； 1) 诱导免疫原性癌细胞死亡的干预措施，2) 对化疗耐药的癌症干细胞中表达的癌症抗原，3) 刺激抗原呈递树突状细胞以激活抗癌 T 细胞的干预措施，4) 激活抗癌 T 细胞的干预措施，5) 逆转癌症诱导的免疫抑制的干预措施。使用小鼠肿瘤模型，我们评估了适当结合上述干预措施的癌症免疫疗法，特别是与免疫检查点阻断疗法。通过未来临床试验的评估，这些结果可能会导致开发出更有效的癌症免疫疗法。

项目成果

Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases.

• DOI: 10.1155/2013/968549
• 发表时间: 2013
• 期刊: Clinical & developmental immunology
• 作者: Qu N;Xu M;Mizoguchi I;Furusawa J;Kaneko K;Watanabe K;Mizuguchi J;Itoh M;Kawakami Y;Yoshimoto T
• 通讯作者: Yoshimoto T

NF-kBシグナルを標的とした卵巣癌局所における免疫抑制環境の改善と治療への応用

靶向NF-kB信号改善卵巢癌局部免疫抑制环境及其治疗应用

• 发表时间: 2013
• 作者: 岩田卓;田中京子;杉山重里;西尾浩;平尾薫丸;森定徹;早川妙香;谷口智憲;河上裕;青木大輔
• 通讯作者: 青木大輔

Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers.

• DOI: 10.1158/1078-0432.ccr-10-2234
• 发表时间: 2011-05-15
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Butterfield LH;Palucka AK;Britten CM;Dhodapkar MV;Håkansson L;Janetzki S;Kawakami Y;Kleen TO;Lee PP;Maccalli C;Maecker HT;Maino VC;Maio M;Malyguine A;Masucci G;Pawelec G;Potter DM;Rivoltini L;Salazar LG;Schendel DJ;Slingluff CL Jr;Song W;Stroncek DF;Tahara H;Thurin M;Trinchieri G;van Der Burg SH;Whiteside TL;Wigginton JM;Marincola F;Khleif S;Fox BA;Disis ML
• 通讯作者: Disis ML

リンパ節微小環境におけるM2マクロファージ分化はCCR4陽性頭頸部がん細胞のリンパ節転移を促進する

淋巴结微环境中M2巨噬细胞分化促进CCR4阳性头颈癌细胞淋巴结转移

• 发表时间: 2012
• 作者: 辻川敬裕;大村学;谷口智憲;小林明日香;川村直;杉山重里;藤田知信;中野宏;島田剛敏;久育男;河上裕
• 通讯作者: 河上裕

Induction of immunoregulatory mesenchymal stem cells by Snail+metastatic tumor cells in bone marrow

Snail骨髓转移瘤细胞诱导免疫调节间充质干细胞

• 发表时间: 2011
• 作者: Kudo Chie;Kawakami Yutaka
• 通讯作者: Kawakami Yutaka