Cancer diagnosis related to immune response against cancer-associated antigen

为了评估癌症患者对癌症相关碳水化合物抗原的体液免疫应答，我们试图产生针对它们的人单克隆抗碳水化合物抗体和抗独特型抗体。制备了抗S_4和抗Lc_4的人源单克隆抗体<M4s>。由于Lc_4抗原在人癌细胞上广泛表达，而编码人源抗Lc_4抗体的免疫球蛋白基因多态性较少，因此我们建立了三株鼠源抗Lc_4抗体的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血清中的抗体时，发现由抗体C5定义的C5独特型在癌症患者血清中比在对照个体血清中显著增加。另一方面，发现由抗体G3定义的G3独特型显著减少， ...更多信息 d在癌症患者的血清中比在对照个体的血清中，如通过统计分析确定的。人源抗Lc_4抗体的VH区大部分由种系基因V_H1.9III编码，而<lambda>人源抗Lc_4抗体的VH区大部分由种系基因V_II.DS编码<lambda>。V_H1.9III和V_II.DS基因的组合<lambda>被广泛用于编码针对Lc_4以外抗原的抗体。其中，C5抗体所定义的C5独特表位由抗Lc_4抗体特异性表达<lambda>，而G3抗体所定义的G3独特表位由抗Lc_4抗体广泛表达<lambda>。这些结果表明，V_H1.9III和V_II.DS基因的组合编码的抗体<lambda>在经常表达Lc_4抗原的癌症患者中主要用于编码针对Lc_4抗原的抗体，而在非癌症患者中，这些基因可以自由地编码针对Lc_4抗原以外的各种外源性抗原的多种抗体。少

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