CHARACTERIZATION OF TCR Vβ RESPONSE TO CANCER ANTIGEN PEPTIDE

TCR Vβ 对癌抗原肽反应的表征

• 批准号: 13671347
• 负责人: ARUGA Atsushi
• 金额: $ 2.37万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671347/
• 关键词: TCR; Vβ; CTL; MUC1; Cancer Vaccine; Synthetic Peptide; Dendritic cell; 癌抗原; TCR Vβ; 抗原ペプチド; 免疫療法; 特異免疫

We have been investigating the immune response of cytotoxic T cells (CTL) with their TCR Vβ repertoire in tumor specific manner. In this study, we investigated the CTL response to synthetic peptide compared with their TCR Vβ repertoire. Synthetic peptide-specific CTLs were generated with in vitro stimulation by peptide-pulsed dendritic cells. When T cells were stimulated with synthetic MUC1 peptide-pulsed DCs, TCR Vβ 1, 2, 3, 7.1 and 17 positive T cells increased after in vitro stimulation. After several injection of MUC1 peptide-pulsed dendritic cells into cancer patients as vaccine, TCR Vβ 1, 2, 3, 7.1 and 17 positive T cells also increased in their peripheral blood. These T cells demonstrated the high cytolytic reactivity against MUC1 positive cancer cell, but not against MUC1 negative cancer cells. IFNγ release from CTLs also increased after vaccination. HLA tetramer could not detect the peptide-specific CTL precursor in vaccinated patients.In conclusion, it was demonstrated that in vivo CTL precursor could be measurable by their TCR Vβ repertoire instead of the examination with common HLA-tetramer staining which is expensive and difficult to make. TCR Vβ repertoire analysis would be useful for the analysis of in vivo CTL precursor in active immunotherapy.

我们研究了细胞毒性T细胞（CTL）及其TCR Vβ库在肿瘤特异性免疫应答中的作用。在本研究中，我们研究了CTL对合成肽的反应，并与它们的TCR Vβ库进行了比较。合成的肽特异性CTL通过肽脉冲的树突状细胞体外刺激产生。当用合成MUC1肽致敏的DC刺激T细胞时，TCR Vβ 1、2、3、7.1和17阳性T细胞在体外刺激后增加。肿瘤患者多次注射MUC1肽致敏的树突状细胞作为疫苗后，外周血中TCR Vβ 1、2、3、7.1和17阳性T细胞也增加。这些T细胞表现出对MUC1阳性癌细胞的高细胞溶解反应性，但对MUC1阴性癌细胞没有。接种后，CTL释放的IFNγ也增加。结论：HLA四聚体染色法不能检测出疫苗免疫后患者体内的肽特异性CTL前体，因此可以通过TCR Vβ库来检测体内CTL前体，而不需要用昂贵且难以制备的普通HLA四聚体染色法来检测。TCRV β库的分析有助于体内CTL前体的分析。

项目成果

有賀 淳: "ここまで進んだガン免疫療法"講談社. 98 (2004)

Atsushi Ariga：“癌症免疫治疗迄今已取得进展”讲谈社 98 (2004)。

有賀 淳: "転移性肺癌に対する免疫的細胞治療"日本臨床. 60(5). 621-624 (2002)

Atsushi Ariga：“转移性肺癌的免疫细胞疗法”日本临床研究 60(5) (2002)。

Naoki Matsumura: "Correlation between expression of MUC1 core protein and outcome after surgery in mass-forming intrahepatic cholangiocarcinoma."Cancer. 94(6). 1770-1776 (2002)

Naoki Matsumura：“MUC1 核心蛋白的表达与肿块性肝内胆管癌手术后结果之间的相关性。”癌症。

Naoki Matsumura: "Correlation between expression of MUC1 core protein and outcome after surgery in mass-forming ICC"Cancer. 94(6). 1770-1776 (2002)

Naoki Matsumura：“MUC1 核心蛋白表达与肿块 ICC 手术后结果的相关性”癌症。

Toshimi Sudoh: "Characterization of effector cells in non-specific cancer immunotherapy."Jpn J Cancer chemother. 30(11). 1817-1820 (2003)

Toshimi Sudoh：“非特异性癌症免疫疗法中效应细胞的表征。”Jpn J Cancer chemother。