Cancer diagnosis related to immune response against cancer-associated antigen

癌症诊断与针对癌症相关抗原的免疫反应有关

• 批准号: 03557114
• 负责人: KANNAGI Reiji
• 金额: $ 8.83万
• 依托单位: Aichi Cancer Center, Research Institute (1992)Kyoto University (1991)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03557114/
• 关键词: anti-carbohydrate antibody; anti-idiotypic antibody; Lc_4; variable region gene; V_H gene; V_<lambda> gene; VH遺伝子; Vλ遺伝子; 単クロ-ン抗体; イディオタイプ; 血清診断

In order to evaluate humoral immune response against cancer-associated carbohydrate antigens in patients with cancer, we tried to generate human monoclonal anti-carbohydrate antibodies and anti-idiotypic antibodies directed to them. Two human monoclonal antibodies, anti-S_<M4s> and anti-Lc_4 anti-bodies, were generated for this purpose. Since the Lc_4 antigen is widely expressed on human cancer cells, and there was less polymorphism in the immunoglobulin genes encoding human anti-Lc_4 antibodies, we established three murine monoclonal anti-idiotypic antibodies (G3, B3 and C5, all IgG) directed against the anti-Lc_4 antibody. When these anti-idiotypic antibodies were used for the detection of serum antibodies in patients with cancers, the C5 idiotype defined by the antibody C5 was found to be significantly in-creased in the sera of cancer patients than in the sera of control individuals. On the other hand, the G3 idiotype defined by the antibody G3 was found to be significantly decrease … More d in the sera of cancer patients than in the sera of control individuals, as ascertained by statistical analysis. Most of the V_H regions of human anti-Lc_4 antibodies were encoded by the germline gene V_H1.9III, while most of the V_<lambda> regions of human anti-Lc_4 antibodies were encoded by the germline gene V_<lambda>II.DS. The combination of V_H1.9III and V_<lambda>II.DS genes were widely used in encoding the antibodies directed to the antigens other than Lc_4. The C5 idiotope defined by the C5 antibody was specifically expressed by the anti-Lc_4 antibodies among these V_H1.9III-V_<lambda>II.DS encoded antibodies, while the G3 idiotope defined by the G3 antibody was widely expressed by these V_H1.9III-V_<lambda>II.DS encoded antibodies directed to the antigens other than Lc_4. These results suggest that the antibodies encoded by the combination of V_H1.9III and V_<lambda>II.DS genes are mostly used to encode antibodies directed to the Lc_4 antigen in patients with cancers which frequently express the antigen, while in patients without cancers, these genes are used freely to encode a wide variety of antibodies which are directed to various exogenous antigens other than the Lc_4 antigen. Less

为了评估癌症患者针对癌症相关碳水化合物抗原的体液免疫反应，我们尝试产生人类单克隆抗碳水化合物抗体和针对它们的抗独特型抗体。为此目的产生了两种人单克隆抗体，抗-S_<M4s>和抗-Lc_4抗体。由于Lc_4抗原在人癌细胞上广泛表达，且编码人抗Lc_4抗体的免疫球蛋白基因多态性较少，因此我们建立了三种针对抗Lc_4抗体的鼠单克隆抗独特型抗体（G3、B3和C5，均为IgG）。当这些抗独特型抗体用于检测癌症患者的血清抗体时，发现由抗体C5定义的C5独特型在癌症患者的血清中比对照个体的血清中显着增加。另一方面，通过统计分析确定，由抗体 G3 定义的 G3 独特型在癌症患者的血清中比在对照个体的血清中显着降低。人抗Lc_4抗体的大部分V_H区由种系基因V_H1.9III编码，而人抗Lc_4抗体的大部分V_λ区由种系基因V_λII.DS编码。 V_H1.9III和V_λII.DS基因的组合广泛用于编码针对Lc_4以外的抗原的抗体。由C5抗体定义的C5独特位由这些V_H1.9III-V_<lambda>II.DS编码的抗体中的抗Lc_4抗体特异性表达，而由G3抗体定义的G3独特位由这些V_H1.9III-V_<lambda>II.DS编码的抗体广泛表达。 Lc_4 以外的抗原。这些结果表明，在经常表达Lc_4抗原的癌症患者中，由V_H1.9III和V_<lambda>II.DS基因组合编码的抗体主要用于编码针对Lc_4抗原的抗体，而在未患癌症的患者中，这些基因被自由地用于编码针对除Lc_4抗原之外的各种外源抗原的多种抗体。 Lc_4抗原。较少的

项目成果

Tuo, X-H, et al.: "Stage-specific expression of cancer-associated type 1 and type 2 chain polylactosamine antigens in the developing pancreas of human embryos." Cancer Res.52. 5744-5751 (1992)

Tuo, X-H 等人：“人类胚胎发育中胰腺中癌症相关 1 型和 2 型链聚乳糖胺抗原的阶段特异性表达。”

神奈木 玲児,銭田 晃一,野吾 和宏: "「糖鎖認識抗体の構造」" BIOmedica. 6(8). 789-795 (1991)

Reiji Kanagi、Koichi Zenida、Kazuhiro Nogo：“碳水化合物链识别抗体的结构”BIOmedica 6(8) (1991)。

Mori,Y.,Hosono,M.,Murakami,K.,Katoh,H.,Yoshikawa,Y.,Kuribayashi,K.,Kannagi,R.,Sakai,M.,Okuma,M.,and Masuda,T.: "Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence s

森 Y.、细野 M.、村上 K.、加藤 H.、吉川 Y.、栗林 K.、神奈木 R.、酒井 M.、大隈 M. 和增田 T。

Kaneko,T,他: "Preparation of mouse-human chimeric antibody to fucosylated stagespecific embryonic antigen-1." J.Biochem.113. 114-117 (1993)

Kaneko，T 等人：“针对岩藻糖基化阶段特异性胚胎抗原 1 的小鼠-人嵌合抗体的制备”，J.Biochem.114-117（1993）。

OHMORI,K.,他: "Differentiation-dependent expression of sialy SSEA-1 and I-antigens on human lymphoid cells and its implications for carbohydrate-mediated adhesion to vascular endothelium." Blood. 81(1). 101-111 (1993)

OHMORI, K. 等人：“唾液酸 SSEA-1 和 I 抗原在人淋巴细胞上的分化依赖性表达及其对碳水化合物介导的血管内皮粘附的影响 81(1)。” (1993)