A novel cancer immunotherapy with down-regulation of regulatory T cells using pretreatment of mild bone marrow suppression.

一种新型癌症免疫疗法，通过轻度骨髓抑制预处理来下调调节性 T 细胞。

• 批准号: 18591474
• 负责人: ITOH Tsuyoshi
• 金额: $ 1.31万
• 依托单位: Kyoto Prefectural University of Medicine
• 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-18591474/
• 关键词: Colorectal Surgery; Cancer vaccine

(1) An effect of mild immunosuppression was observed in mice administered cyclophosphamide. Cytotoxic T lymphocyte (CTL) response was enhanced in mice with this pretreatment possibly due to the down regulation of regulatory T cells which is considered to drive T helper-2 (112) immune response.(2) The administration of anti-CD40 ligand monoclonal antibody (mAb) augmented this CTL response.(3) Cancer vaccine protocol using the pretreatment of cyclophosphamide and the administration of a CD40L was evaluated as for its CTL response as well as anti tumor effect. C57B1/6 mice immunized with S11NFEKT peptide using this vaccine protocol were challenged with B16-0UA tumor cell lines. An enhancement of peptide-specific CTL response and anti tumor effect was observed. Its anti tumor effect was strongest in mice immunized with peptide concomitantly given cyclophosphamide and a-CD4OL Although some response was demonstrated in mice immunized with peptide alone, cyclophosphamide and a-CD40L elicited more strong peptide specific CM response and rejected tumor challenged after vaccination.In conclusion, pretreatment of cyclophophamide and a-CD40L aiming at the down regulation of regulatory T cells enhanced peptide specific T cell response and effectively elicited anti tumor response. This vaccine protocol may be the break through for optimal cancer vaccine therapy.

(1)在给予环磷酰胺的小鼠中观察到轻度免疫抑制作用。在这种预处理的小鼠中，细胞毒性T淋巴细胞（CTL）应答增强，可能是由于调节性T细胞的下调，调节性T细胞被认为是驱动T辅助细胞-2（112）免疫应答的原因。(2)抗CD 40配体单克隆抗体（mAb）的管理增强了这种CTL应答。(3)评价了使用环磷酰胺预处理和施用CD 40 L的癌症疫苗方案的CTL应答以及抗肿瘤效果。使用该疫苗方案用S11 NFEKT肽免疫的C57 B1/6小鼠用B1/6 - 0 UA肿瘤细胞系攻击。观察到肽特异性CTL应答和抗肿瘤效应的增强。结果表明，环磷酰胺和α-CD 40 L联合免疫的小鼠，其抗肿瘤作用最强，而环磷酰胺和α-CD 40 L联合免疫的小鼠，其抗肿瘤作用更强。针对下调调节性T细胞的环磷酰胺和α-CD 40 L预处理增强了肽特异性T细胞应答，并有效地引发抗肿瘤应答。该疫苗方案可能是最佳癌症疫苗治疗的突破。

项目成果

Induction of peptide-specific immune response in patients with primary malignant melanoma of the esophagus after immunotherapy using dendritic cells pulsed with MAGE peptides.

• DOI: 10.1093/jjco/hyl136
• 发表时间: 2007-02
• 期刊: Japanese journal of clinical oncology
• 影响因子: 2.4
• 作者: Y. Ueda;K. Shimizu;Tsuyoshi Itoh;N. Fuji;K. Naito;A. Shiozaki;Yoshiki Yamamoto;Takeshi Shimizu;Arihiro Iwamoto;H. Tamai;H. Yamagishi

Outcomes of supervised surgical training for the resection of colo-rectal cancer

结直肠癌切除手术监督培训的结果

• 发表时间: 2007
• 作者: Itoh T;Fuji N;et. al.
• 通讯作者: et. al.

Successful induction of clinically competent dendritic cells from glanulocyte colony-stimulating factor-mobilized monocytes for cancer vaccine therapy

从粒细胞集落刺激因子动员的单核细胞成功诱导临床活性树突状细胞用于癌症疫苗治疗

• 发表时间: 2006
• 作者: Itoh;T
• 通讯作者: T

Successful induction of clinically competent dendritic cells from granulocvte colony-stimulating factor-mobilized monocvtes for cancer vaccine therapy

从粒细胞集落刺激因子动员的单核细胞成功诱导临床活性树突状细胞用于癌症疫苗治疗

• 发表时间: 2007
• 期刊: Cancer Immunology Immunotherapy 56(3)
• 作者: Ueda Y;Itoh T;Fuli N;et. al.
• 通讯作者: et. al.

Port site herniation of the small bowel following laparoscopy-assisted distal gastrectomy: a case report.

• DOI: 10.1186/1752-1947-2-48
• 发表时间: 2008-02-14
• 期刊: Journal of medical case reports
• 影响因子: 1
• 作者: Itoh, Tsuyoshi;Fuji, Nobuaki;Naito, Kazuyo
• 通讯作者: Naito, Kazuyo