Development of novel cancer therapy by combination of immune activation with tumor apoptosis induction

通过免疫激活与肿瘤细胞凋亡诱导相结合开发新型癌症疗法

• 批准号: 20590494
• 负责人: KAZUYOSHI Takeda
• 金额: $ 3.08万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590494/
• 关键词: 免疫監視; 腫瘍免疫; 癌治療; 細胞死; 免疫活性化; 免疫抑制; regulatory T細胞; 所属リンパ節; CTL; CTLA-4; アポトーシス; Tim-3; CD8α^+樹状細胞; トレランス; C-ERC; mesotheli; ADCC; 中皮腫; NK細胞; TRAIL; DR5; CD40; CD137; IL-15; Erb-2; HER2; histone deacetylase inhibitor; bortezomib

TrimAb is the antibody cocktail therapy combining tumor apoptosis-inducing therapy with immune-activating therapy. We have here found that trimAb synergistically eradicated tumors when combined with several kinds of anti-tumor molecular targeting reagents that were already applied to clinical treatment. Suppression of immune inhibitory responses due to phagocytosis of apoptotic tumor cells is possibly useful to augment immune therapies against cancers. Moreover, based on the results of combination with several therapies targeting immune inhibition, we revealed that improvement of immune environment in tumor mass is the most critical to augment specific anti-tumor immune responses inducing tumor rejection.

TrimAb 是一种抗体鸡尾酒疗法，结合了肿瘤细胞凋亡诱导疗法和免疫激活疗法。我们发现，trimAb与多种已应用于临床治疗的抗肿瘤分子靶向试剂联合使用，可以协同消灭肿瘤。由于凋亡肿瘤细胞的吞噬作用而抑制免疫抑制反应可能有助于增强针对癌症的免疫治疗。此外，根据与几种针对免疫抑制的疗法相结合的结果，我们发现改善肿瘤块中的免疫环境对于增强诱导肿瘤排斥的特异性抗肿瘤免疫反应是最关键的。

项目成果

Organ microenvironment plays significant roles through Fas ligand in vaccine-induced CD4^+ T cell dependent suppression of tumor grow that the orthotopic site.

器官微环境通过 Fas 配体在疫苗诱导的 CD4^T 细胞依赖性肿瘤生长抑制中发挥重要作用。

• 发表时间: 2010
• 作者: Sugiura; D.; et al.
• 通讯作者: et al.

Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation.

Tim-3 介导凋亡细胞的吞噬作用和交叉呈递。

• 发表时间: 2009
• 作者: Nakayama M.; Akiba H.; Takeda K.; 他
• 通讯作者: 他

抗体カクテル療法による癌治療

使用抗体鸡尾酒疗法治疗癌症

• 发表时间: 2009
• 作者: 竹田和由

Roles of PU.1 in monocyte-and mast cell-specific gene regulation : PU.1 transactivates CIITA pIV in cooperation with IFN-γ

PU.1 在单核细胞和肥大细胞特异性基因调控中的作用：PU.1 与 IFN-γ 配合反式激活 CIITA pIV

• 发表时间: 2009
• 作者: Ito; T.
• 通讯作者: T.

Co-inhibitory roles for glucocorticoid-induced TNF receptor in CDld-dependent natural killer T cells.

CD1d依赖性自然杀伤T细胞中糖皮质激素诱导的TNF受体的共抑制作用。

• 发表时间: 2008
• 作者: Chen; S.
• 通讯作者: S.