Specific immunotherapy against cancer using adenocarcinoma restricted antigen peptide that is recognized by human monoclonal antibody.

使用人单克隆抗体识别的腺癌限制性抗原肽针对癌症进行特异性免疫治疗。

• 批准号: 11671150
• 负责人: TAKIGUCHI Nobuhiro
• 金额: $ 1.92万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671150/
• 关键词: Human Monoclonal Antibody; cancer associated antigen; cDNA cloning; colon cancer; AgSK1; specific immunotherapy; cytotoxic T lymphocyte; peptide vaccine; 細胞障害性T細胞(CTL); ペプチド抗原; 抗イディオタイプ抗体; 細胞傷害性T細胞(CTL); 癌ワクチン

SK1, a human IgM monoclonal antibody recognizes the antigen, termed AgSK1, which was shown to be preferentially expressed by human adenocarcinomas, particularly human gastrointestinal malignancies (Bt.J.Camcer 78, 1313-22, 1998). Recently, we screened a cDNA expression library constructed using mRNA from a colon carcinoma cell line HT29 and isolated a partial cDNA clone designated AgSK1-2HT ( Tissue Antigens 55, 157-61, 2000). This clone consisted of an amino terminal open reading frame of 54 amino acids and the carboxyl terminal 20 amino acids of this coding region contained the antigenic epitope recognized by SK1. In order to show additional evidence for our claim that the identified peptide was the main antigenic epitope recognized by SK1, we tried to determine a full length cDNA sequence of this clone. Searching the nonredundant and EST database using the BLAST program, we found a clone DJ1129D05 that contained a highly homologous fragment to the coding region of AgSK1-2HT.According to the sequence of this clone, we PCR amplified several overlapping fragments using mRNA from a human colon carcinoma cell line LoVo and directly sequenced them. Assembly of these sequences yielded the entire coding sequence of AgSK1-2HT that seemed have 387 nucleotides encoding 129 amino acid peptide ( NCBI Gen Bank accession number AF316855 and AAK15476). We also found that this clone consisted of 9-mer and 10-mer peptide which carried the strong allele specific anchor residues to HLA-A2402 and HLA-A0201 respectively. We are now trying to induce CTL using these peptides in vitro. Although we should further analyze these peptides, AgSK1-2HT may be utilized as a useful cancer vaccine.

SK 1是一种人IgM单克隆抗体，识别称为AgSK 1的抗原，其显示优先由人腺癌，特别是人胃肠道恶性肿瘤表达（Bt.J.Camcer 78，1313-22，1998）。最近，我们筛选了使用来自结肠癌细胞系HT 29的mRNA构建的cDNA表达文库，并分离了命名为AgSK 1 - 2 HT的部分cDNA克隆（Tissue Antigens 55，157-61，2000）。该克隆由54个氨基酸的氨基端开放阅读框组成，该编码区的羧基端20个氨基酸含有SK 1识别的抗原表位。为了证明我们所鉴定的肽是SK 1识别的主要抗原表位，我们试图确定该克隆的全长cDNA序列。通过BLAST程序检索非冗余数据库和EST数据库，发现一个与AgSK 1 - 2 HT编码区高度同源的克隆DJ 1129 D 05，并根据该克隆的序列，从人结肠癌细胞株LoVo的mRNA中扩增出几个重叠片段，直接测序。这些序列的组装产生了AgSK 1 - 2 HT的完整编码序列，其似乎具有387个核苷酸，编码129个氨基酸的肽（NCBI Gen Bank登录号AF 316855和AAK 15476）。我们还发现该克隆由9-mer和10-mer肽组成，分别携带HLA-A2402和HLA-A0201的强等位基因特异性锚残基。我们现在正试图在体外使用这些肽诱导CTL。虽然我们还需要进一步分析这些肽，但AgSK 1 - 2 HT可能用作有用的癌症疫苗。

项目成果

Jun Yasutomi, et al.: "Identification of the Immunoreactive Peptide Sequence for AgSK1, an Adenocarcinoma-Restricted Antigen."Tissue Antigens. 55. 157-61 (2000)

Jun Yasutomi 等人：“腺癌限制性抗原 AgSK1 的免疫反应肽序列的鉴定”。组织抗原。

Soda,H.et al.: "Adoptive immunotherapy for advanced cancer patients using in vitro activated cytotoxic Tlymphocytes."Journal of Surgical Oncology. 72(4). 211-217 (1999)

Soda, H. 等人：“使用体外激活的细胞毒性 T 淋巴细胞对晚期癌症患者进行过继免疫治疗。”《肿瘤外科杂志》。

Mark C.Glassy et al.: "Lessons learned about the therapeutic potential of the natural human immune response to lung cancer."Exp.Opin.Invest.Drugs. 8. 995-1006 (1999)

Mark C.Glassy 等人：“我们学到了人类自然免疫反应对肺癌的治疗潜力。”Exp.Opin.Invest.Drugs。

Yasutomi,J. et al.: "Identification of immunoreactive peptide sequence for AgSK1, an adenocarcinoma-restricted antigen."Tissue Antigens. 55(2). 157-161 (2000)

安富，J.

J. Yasutomi et al.: "Identification of the immunoreactive peptide sequence for AgSK1, an adenocarcinoma-restricted antigen"Tissue Antigens. 55・2. 157-161 (2000)

J. Yasutomi 等：“腺癌限制性抗原 AgSK1 的免疫反应肽序列的鉴定”组织抗原 55·2（2000）。