Development of pancreatic cancer vaccine therapy using genetically modified dendritic cells via ubiquitin-proteasome pathway

通过泛素-蛋白酶体途径使用转基因树突状细胞开发胰腺癌疫苗疗法

• 批准号: 20790964
• 负责人: OJIMA Toshiyasu
• 金额: $ 1.75万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 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-20790964/
• 关键词: 樹状細胞; 細胞傷害性T細胞; メソテリン; ユビキチン; アデノウイルスベクター

Mesothelin (MSLN) is an attractive candidate as a molecular target for pancreatic cancer immunotherapy. The purpose of this study was to demonstrate that cytotoxic T lymphocytes (CTLs) generated from peripheral blood mononuclear cells (PBMCs) by stimulation with genetically-modified dendritic cells (DCs) expressing MSLN could produce specific anti-tumor immunity against pancreatic cancer cells endogenously expressing MSLN. MSLN-specific CTLs induced by in vitro stimulation with DC-AxCAMSLN killed pancreatic cancer cell lines expressing MSLN in an HLA-restricted fashion. These CTLs also showed cytotoxic activity against autologous LCL pulsed with multiple MSLN-derived epitope peptides. In addition, CD8+ T cells, as well as CD4+ T cells, sorted from these CTLs showed significant production of interferon-gannma when stimulated with DC-AxCAMSLN. These results therefore suggest the potential of developing future clinical applications of the vaccines using genetically-modified DCs expressing MSLN.

间皮素（MSLN）是胰腺癌免疫治疗的一个有吸引力的候选分子靶点。本研究的目的是证明通过用表达MSLN的基因修饰的树突状细胞（DC）刺激从外周血单核细胞（PBMC）产生的细胞毒性T淋巴细胞（CTL）可以产生针对内源性表达MSLN的胰腺癌细胞的特异性抗肿瘤免疫。通过用DC-AxCAMSLN体外刺激诱导的MSLN特异性CTL以HLA限制性方式杀死表达MSLN的胰腺癌细胞系。这些CTL还显示出针对用多种MSLN衍生的表位肽脉冲的自体LCL的细胞毒性活性。此外，当用DC-AxCAMSLN刺激时，从这些CTL分选的CD 8 + T细胞以及CD 4 + T细胞显示出显著的干扰素-gannma产生。因此，这些结果表明使用表达MSLN的遗传修饰的DC开发疫苗的未来临床应用的潜力。

项目成果

Evaluation of Double Tract Reconstruction After Total Gastrectomy in Patients with Gastric Cancer: Prospective Randomized Controlled Trial

• DOI: 10.1007/s00268-009-0109-0
• 发表时间: 2009-09-01
• 期刊: WORLD JOURNAL OF SURGERY
• 影响因子: 2.6
• 作者: Iwahashi, Makoto;Nakamori, Mikihito;Yamaue, Hiroki
• 通讯作者: Yamaue, Hiroki

Tumor vaccine therapy against recrudescent tumor using dendritic cells simultaneously transfected with tumor RNA and granulocyte macrophage colony-stimulating factor RNA

• DOI: 10.1111/j.1349-7006.2007.00698.x
• 发表时间: 2008-02-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Naka, Teiji;Iwahashi, Makoto;Yamaue, Hiroki
• 通讯作者: Yamaue, Hiroki

CpG-ODNによる癌抗原特異的エフェクター細胞の効率的誘導と抗腫瘍活性増強効果

CpG-ODN 有效诱导癌症抗原特异性效应细胞并增强抗肿瘤活性

• 发表时间: 2009
• 作者: 勝田将裕;岩橋誠;中森幹人;中村公紀;松田健司;中禎二;尾島敏康;飯田武;宮澤基樹;角田卓也;中村祐輔;山上裕機
• 通讯作者: 山上裕機

Clinicopathological Characteristics of Remnant Gastric Cancer After a Distal Gastrectomy

• DOI: 10.1007/s11605-009-1090-5
• 发表时间: 2010-02-01
• 期刊: JOURNAL OF GASTROINTESTINAL SURGERY
• 影响因子: 3.2
• 作者: Ojima, Toshiyasu;Iwahashi, Makoto;Yamaue, Hiroki
• 通讯作者: Yamaue, Hiroki

進行食道癌に対するCpG-B併用新規腫瘍抗原ペプチドワクチン療法:第I相臨床試験の結果からみた将来展望

新型肿瘤抗原肽疫苗联合CpG-B治疗晚期食管癌：I期临床试验结果展望未来

• 发表时间: 2009
• 作者: 岩橋誠;勝田将裕;中森幹人;中村公紀;飯田武;中禎二;尾島敏康;松田健司;角田卓也;中村祐輔;山上裕機
• 通讯作者: 山上裕機