Immunological response against bone and soft tissue sarcoma

针对骨和软组织肉瘤的免疫反应

• 批准号: 22689041
• 负责人: TSUKAHARA Tomohide
• 金额: $ 16.39万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22689041/
• 关键词: 骨; 軟部腫瘍学; 骨肉腫抗原; HLA/ペプチド複合体; ファージディスプレイライブラリ

We performed phase I clinical peptide vaccination trial for patient with osteosarcoma. We used HLA-A24 or HLA-A2-restricted PBF-derived peptides as the vaccines with incomplete Freund' adjuvant. The peptide-specific CTL responses were observed in two HLA-A24+ and one HLA-A2+patients. After the confirmation of safety and immunogenicity of the peptide vaccines, we will plan phase II trial as adjuvant therapy after operative resection combined with post-operative chemotherapy.In addition, we generated artificial antibody against HLA/peptide complex recognized by CTL(natural epitope antibody). scFv phage display library was constructed from RNA derived from human naive PBMC and tonsiles, followed by biopanning using HLA-A2/PBF peptide complex. After panning, one scFv clone was obtained and converted into hIgG1 subtype(scFv-hIgG1). The scFv-hIgG1 recognized peptide-pulsed T2 cells by FACS and showed high affinity by SPR analysis. This natural epitope antibody might be useful for the detection of HLA/peptide complex on tumor cells and for the development of genetically engineered CTLs expressing natural epitope antibody for adoptive cell therapy.

我们对骨肉瘤患者进行了一期临床多肽疫苗接种试验。我们用人类白细胞抗原A24或人类白细胞抗原A2限制性的PBF衍生肽作为不完全弗氏佐剂的疫苗。在2例人类白细胞抗原A24+和1例人类白细胞抗原A2+患者中观察到多肽特异性CTL反应。在确认多肽疫苗的安全性和免疫原性后，我们将计划进行II期试验，作为手术切除后的辅助治疗结合术后的化疗。此外，我们还产生了针对CTL(自然表位抗体)识别的人类白细胞抗原/多肽复合体的人工抗体。从人未成熟的PBMC和扁桃体中提取RNA，构建单链抗体噬菌体展示文库，然后用人类白细胞抗原A2/PBF多肽复合物进行生物筛选。平皿筛选后获得1个scFv克隆，转化为hIgG1亚型(scFv-hIgG1)。FACS检测表明，ScFv-hIgG1可识别多肽冲击的T2细胞，SPR分析显示其具有较高的亲和力。该天然表位抗体可用于检测肿瘤细胞表面的人类白细胞抗原/多肽复合体，并可用于开发表达天然表位抗体的基因工程CTL，用于过继细胞治疗。

项目成果

骨軟部肉腫に対するペプチドワクチン療法

骨和软组织肉瘤的肽疫苗治疗

• 发表时间: 2015
• 作者: Michifuri Y;Hirohashi Y;Torigoe T;Miyazaki A;Fujino J;Tamura Y;Tsukahara T;Kanaseki T;Kobayashi J;Sasaki T;Takahashi A;Nakamori K;Yamaguchi A;Hiratsuka H;Sato N.;塚原 智英;塚原 智英
• 通讯作者: 塚原 智英

Generation of TCR-like antibody against HLA/peptide complex of an osteosarcoma antigen PBF

针对骨肉瘤抗原 PBF 的 HLA/肽复合物生成 TCR 样抗体

• 发表时间: 2011
• 作者: 塚原智英;鳥越俊彦;佐藤昇志;和田卓郎
• 通讯作者: 和田卓郎

Generation of TCE-like antibody against HLA/peptide complex of an osteosarcoma antigen PBF「ワークショップ48:がん免疫療法」

针对骨肉瘤抗原 PBF 的 HLA/肽复合物生成 TCE 样抗体“研讨会 48：癌症免疫疗法”

• 发表时间: 2011
• 作者: 塚原智英;ほか
• 通讯作者: ほか

ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells

• DOI: 10.1093/carcin/bgs118
• 发表时间: 2012-05-01
• 期刊: CARCINOGENESIS
• 影响因子: 4.7
• 作者: Matsuzaki, Junichi;Torigoe, Toshihiko;Sato, Noriyuki
• 通讯作者: Sato, Noriyuki