Analyses for the enhancing methods of tumor vaccination therapy in cancer-bearing hosts

癌症宿主肿瘤疫苗接种治疗的强化方法分析

• 批准号: 18591241
• 负责人: SHIBAGAKI Naotaka
• 金额: $ 2.49万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591241/
• 关键词: Vaccine; Antigen-specific immune responses; Antigen presentation; Protein transduction; 免疫療法; 樹状細胞; タンパク抗原

We previously have shown that nona-arginine (R9)-PTD induced efficient protein-antigen (Ag) transduction of dendritic cells (DCs) in vitro, resulting in the efficient induction of strong Ag-specific immune responses mediated by CD8+ and CD4+ T cells and in superior antitumor effects in vivo. In the present study, we investigated the immune responses caused by intradermal (i.d.) injections of R9-PTD-containing protein Ags without DC preparation. We found that i.d. injections of recombinant R9-ovalbumin fusion protein (rR9-OVA) into naive C57BL/6 mice elicited OVA-specific CTLs and produced IgG2-dominant immunoglobulin. The i.d. injections of rR9-OVA also induced inflammatory cell infiltrations containing neutrophils, monocytes, and lymphocytes, as well as inflammatory cytokine productions, such as IFN-gamma, IL-2, IP-10, with presenting SIINFEKL-epitopes on MHC class I molecules at the injection area. Intratumoral injections of rR9-OVA into EG.7-tumor mass significantly suppressed tumor growth, and these effects were completely abrogated by the depletion of CD8+ T cells. These results indicate that i.d. injections of rR9-containing immunogenic Ag simultaneously induce dual immunological effects: the induction of Tc1- and Th1-dominant immune responses, and the induction of inflammatory and CTL-mediated immune responses at the injection area by expressing Ag-epitopes onto MHC class I molecules as targets.

我们先前已经证明，诺纳-精氨酸(R9)-PTD在体外可以有效地诱导树突状细胞(DC)蛋白抗原(Ag)转导，从而有效地诱导CD8+和CD4+T细胞介导的强大的Ag特异性免疫应答，并在体内产生优越的抗肿瘤效果。在本研究中，我们研究了皮内注射(I.D.)引起的免疫反应。注射含R9-PTD的蛋白AGS，不需要DC制备。我们找到了那个身份证。将重组R9-卵清蛋白融合蛋白(rR9-OVA)注射到幼龄C57BL/6小鼠体内，可诱导出OVA特异性CTL，并产生以IgG2为主的免疫球蛋白。身份证明。注射rR9-OVA还诱导炎性细胞浸润，包括中性粒细胞、单核细胞和淋巴细胞，以及炎性细胞因子如干扰素-γ、IL-2、IP-10的产生，并在注射区域呈现MHC-I类分子上的SIINFEKL表位。瘤内注射rR9-OVA可显著抑制肿瘤生长，这种作用可被CD8+T细胞耗尽所完全消除。这些结果表明，身份识别。同时注射含有rR9的免疫原性抗原可以产生双重免疫效应：诱导以Tc1和Th1为主的免疫应答，以及通过在MHC-I类分子上表达抗原表位，在注射部位诱导炎症和CTL介导的免疫应答。

项目成果

Polyarginine-mediated protein delivery to dendritic cells presents antigen more efficiently onto MHC class I and class II

聚精氨酸介导的蛋白质递送至树突状细胞，更有效地将抗原呈递至 MHC I 类和 II 类

• 发表时间: 2006
• 期刊: Jouranal of Investigative Dermatology 126(8)
• 作者: Mitsui H;Inozume T;Kitamura R;Shibagaki N;shimada S.
• 通讯作者: shimada S.

Human eosinophils have an intact signaling pathway leading to a major transforming growth factor-beta target gene expression.

人类嗜酸性粒细胞具有完整的信号通路，导致主要的转化生长因子-β靶基因表达。

• 发表时间: 2007
• 期刊: International Archives of Allergy and Immunology 142
• 作者: M. Kanzaki;N. Shibagaki;et. al.
• 通讯作者: et. al.

Dendritic cells transduced with autoantigen FCRLA induce cytotoxic lymphocytes and vaccinate against murine B-Cell lymphoma

• DOI: 10.1038/sj.jid.5700909
• 发表时间: 2007-12-01
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Inozume, Takashi;Mitsui, Hiroshi;Shimada, Shinji
• 通讯作者: Shimada, Shinji

Human eosinophils have an intact Smad signaling pathway leading to a major transforming growth factor-beta traget gene expression

人类嗜酸性粒细胞具有完整的 Smad 信号通路，导致主要的转化生长因子-β 目标基因表达

• 发表时间: 2006
• 期刊: International Archive of Allegy and Immunology 142(4)
• 作者: Kanzaki M;Shibagaki N;Hatsushika K;Mitsui H;Inozume T Okamoto A;Dobashi Y;Ogawa H;Shimada S;Nkao A.
• 通讯作者: Nkao A.

Human eosinophils have an intact signaling pathway leading to a major transforming growth factor-beta target gene expression

人类嗜酸性粒细胞具有完整的信号通路，导致主要的转化生长因子-β靶基因表达

• 发表时间: 2007
• 期刊: International Archives of Allergy and Immunology 142(4)
• 作者: M. Kanzaki;N. Shibagaki;et. al.
• 通讯作者: et. al.