Investigation for the specific cancer immunotherapy using antigens recognized by a human natural antibody and the anti-idiotypic antibodies

使用人类天然抗体识别的抗原和抗独特型抗体研究特异性癌症免疫疗法

• 批准号: 13671215
• 负责人: KODA Keiji
• 金额: $ 2.18万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671215/
• 关键词: human monoclonal antibody; SK1; cancer immunotherapy; anti-idiotypic antibody; colon cancer; breast cancer; 特異的癌免疫治療; ペプチドワクチン; AgSK1

SK1 is an IgM human monoclonal antibody which recognizes a widely expressed glycoprotein antigen found on adenocarcinoma tissues. The antigen recognized by SK-1 (AgSK1) has a molecular weight of 42-46 kilodaltons and is strongly expressed on cells with high invasion capacity. We have recently identified a peptide sequence that is recognized by SK1. The antigen consisted of 54 amino acids and carboxyl terminal 20 amino acids were the antigenic epitope of SK1. The RT-PCR to determine the quantity of the AgSK1 in the panel of the human tissues revealed that the quantity of the mRNA level which encoded the AgSK1 was high in colon cancer cell lines and tissues. Whereas there was quite low or even no amount of the mRNA level found in non-epithelial tumor cell lines or in the normal colon mucosa, blood of no-cancer-bearing cases. These findings were consistent with the AgSK1 protein level in several tissues and cell lines determined by immunohistochemistry or Western blotting. We are now constructing a fibroblast cell line that had originally no AgSK1 detected but have expressed high level of AgSK1 by gene transduction. The invasion or motility capacity of the fibroblast and the inhibitory effect of this cell line by SK1 is now under investigation.

SK 1是一种IgM型人单克隆抗体，可识别腺癌组织中广泛表达的糖蛋白抗原。SK-1识别的抗原（AgSK 1）具有42-46千道尔顿的分子量，并且在具有高侵袭能力的细胞上强烈表达。我们最近已经确定了一个肽序列，是由SK 1识别。该抗原由54个氨基酸组成，羧基端20个氨基酸为SK 1的抗原表位。RT-PCR测定人组织组中AgSK 1的量显示，编码AgSK 1的mRNA水平的量在结肠癌细胞系和组织中较高。而在非上皮性肿瘤细胞系或正常结肠粘膜、非癌病例血液中的mRNA水平很低甚至没有。这些发现与免疫组化或Western印迹法测定的几种组织和细胞系中的AgSK 1蛋白水平一致。我们现在正在构建一个成纤维细胞系，原来没有检测到AgSK 1，但通过基因转导高水平表达AgSK 1。目前正在研究成纤维细胞的侵袭或运动能力以及SK 1对该细胞系的抑制作用。

项目成果

Glassy M, Koda K: "The nature of an ideal therapeutic human antibody"Expert. Opin. Biol. Ther.. 2(1). 1-2 (2002)

Glassy M、Koda K：“理想的治疗性人类抗体的本质”专家。

Koda K, Miyazaki M: "Clinical assessment of monoclonal antibodies for the treatment and diagnosis of colorectal cancers"Nippon Rinsho. 60(3). 539-544 (2002)

Koda K、Miyazaki M：“单克隆抗体治疗和诊断结直肠癌的临床评估”Nippon Rinsho。

幸田圭史, 他: "大腸癌に対するモノクローナル抗体を用いた診断と治療の現況"日本臨床. 60(3). 539-544 (2002)

Keishi Koda 等：“使用单克隆抗体诊断和治疗结直肠癌的现状”日本临床研究 60(3) (2002)。

Keiji Koda, Mark C. Glassy, Michael E. McKnight, Jun Yasutomi, Norio Saito, Michael Dan, and Nobuyuki Nakajima: "Immunotherapy for recurrent colorectal cancers with human monoclonal antibody SK-1"Anticancer Res.. 21(1B). 621-627 (2001)

Keiji Koda、Mark C. Glassy、Michael E. McKnight、Jun Yasutomi、Norio Saito、Michael Dan 和 Nobuyuki Nakajima：“用人单克隆抗体 SK-1 进行复发性结直肠癌的免疫治疗”抗癌研究 21(1B)。

Kondo E, Koda K, Takiguchi N, Oda K, Seike K, Ishizuka M, Miyazaki M: "Preoperative natural killer cell activity as a prognostic factor for distant metastasis following surgery for colon cancer"Digest Surg.. in press. (2003)

Kondo E、Koda K、Takiguchi N、Oda K、Seike K、Ishizuka M、Miyazaki M：“术前自然杀伤细胞活性作为结肠癌手术后远处转移的预后因素”消化外科杂志正在出版。