Identification of epithelial cancer-associated antigens and application to cancer vaccine

上皮癌相关抗原的鉴定及其在癌症疫苗中的应用

• 批准号: 13671267
• 负责人: HARADA Mamoru
• 金额: $ 2.3万
• 依托单位: Kurume 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-13671267/
• 关键词: tumor immunology; tumor antigen; peptide; vaccine; がん免疫; 免疫療法; CD4陽性T細胞

1. HLA-DRB1*04501-restricted CD4+ T cells recognizing B cell and monocytic lymphoma cells were established from carcinomatous peritoneal cells from a ovarian cancer. Because these CD4+ T cells showed autoreactivity, antigen cloning with cDNA library was impossible. However, during the experiment, plasmids expressing invariant chain (Ii) or class II transactivator (CIITA) gene were prepared.2. In clinical trials conducted in Kurume University, its has been observed that IgG reactive to administered 9-mer or 1 0-mer peptide could be induced in vaccinated cancer patients. The author reported that vaccination with a UBE2V43-51 peptide into a lung cancer patient resulted in the in vivo induction of UBE2V43-51 peptide-recognizing and HLA-DRB1*0403-restricted CD4+ T cells.3. The author identified that PSA152-160 and PSA248-257 peptides can induce prostate cancer-reactive CTLs in HLA-A24+ prostate cancer patients. In addition, the author identified long PSA peptide-recognizing CD4+ T cells from a prostate cancer patient who received peptide vaccination with the PSA248-257 peptide and showed an increase level of IgG reactive to the PSA248-257 peptide. These CD4+ T cells and IgG which increased after the peptide vaccination showed no reactivity against the administered PSA248-257 peptide, suggesting epitope spreading of both CD4+ T cells and IgG.

1.从来自卵巢癌的癌性腹膜细胞建立识别B细胞和单核细胞淋巴瘤细胞的HLA-DRB 1 *04501限制性CD 4 + T细胞。由于这些CD 4 + T细胞具有自身反应性，因此无法用cDNA文库克隆抗原。然而，在实验过程中，表达不变链（Ii）或II类反式激活因子（CIITA）基因的质粒被破坏.在Kurdom University进行的临床试验中，已经观察到，在接种疫苗的癌症患者中可以诱导与施用的9-mer或10-mer肽反应的IgG。作者报道了将UBE 2 V43 -51肽接种到肺癌患者体内导致体内诱导识别UBE 2 V43 -51肽和HLA-DRB 1 *0403限制性CD 4 + T细胞。作者发现PSA 152 -160和PSA 248 -257肽可以在HLA-A24+前列腺癌患者中诱导前列腺癌反应性CTL。此外，作者从接受PSA 248 - 257肽疫苗接种的前列腺癌患者中鉴定了长PSA肽识别CD 4 + T细胞，并显示出对PSA 248 -257肽反应的IgG水平增加。这些在肽疫苗接种后增加的CD 4 + T细胞和IgG显示出对施用的PSA 248 -257肽没有反应性，表明CD 4 + T细胞和IgG两者的表位扩散。

项目成果

Harada, M.: "Use of an in vitro immunoselected tumor line to identify shared melanoma antigens recognized by HLA-A^*0201-restricted T cells"Cancer Research. 61. 1089-1094 (2001)

Harada, M.：“使用体外免疫选择肿瘤系来识别 HLA-A^*0201 限制性 T 细胞识别的共享黑色素瘤抗原”癌症研究。

Tanaka K.: "Serin proteinase inhibitor 9 as a tumor antigen recognized by cytotoxic T lymphocytes of epithelial cancer patients."Jpn.J.Cancer Res.. 93. 198-208 (2002)

Tanaka K.：“丝氨酸蛋白酶抑制剂 9 作为上皮癌患者的细胞毒性 T 淋巴细胞识别的肿瘤抗原。”Jpn.J.Cancer Res.. 93. 198-208 (2002)

Itoh K.: "Squamous cell and adeno cancer antigens recognized by cytotoxic T lymphocyte"Taylor & Francis Publishers. 22 (2003)

Itoh K.：“细胞毒性 T 淋巴细胞识别鳞状细胞和腺癌抗原”Taylor

Harada M.: "Evidence of extrathymic development of TRP-2-recognizing CD8^+ T cells with low avidity."Immunology. 104. 67-74 (2001)

Harada M.：“低亲和力的 TRP-2 识别 CD8^ T 细胞的胸腺外发育的证据。”免疫学。

Ishihara Y.: "HER2/neu-derived peptides recognized by both cellular and humoral immune responses in HLA-A2^+ cancer patients."Int.J.Oncol.. 24. 967-975 (2004)

Ishihara Y.：“HLA-A2^ 癌症患者的细胞和体液免疫反应均识别 HER2/neu 衍生肽。”Int.J.Oncol.. 24. 967-975 (2004)