Cancer diagnosis related to immune response against cancer-associated antigen

为了评估癌症患者对肿瘤相关碳水化合物抗原的体液免疫应答，我们试图制备针对它们的人源性抗碳水化合物单抗和抗独特型抗体。为此，制备了两种人源性单抗：抗S M4s&gt和抗LC_4抗体。鉴于人癌细胞广泛表达LC_4抗原，且人抗LC_4抗体编码的免疫球蛋白基因多态性较低，我们建立了三种针对抗LC_4抗体的小鼠抗独特型单抗(G3、B3和C5，均为免疫球蛋白G)。当用这些抗独特型抗体检测癌症患者血清抗体时，发现癌症患者血清中由抗体C5定义的C5独特型显著高于对照组。另一方面，由抗体G3定义的G3独特型被发现显著降低…经统计分析证实，癌症患者血清中的D含量高于对照组。人抗LC_4抗体的V_H区大部分由胚系基因V_H1.9III编码，而人抗LC_4抗体的V_H区大部分由胚系基因V_lt；lambda&gt；ii DS编码。在这些V_H1.9III-V_&lt；IiiDS编码的抗体中，由抗LC4抗体特异表达的C5独特位；而由G3抗体定义的G3独特位则广泛地由这些V_H1.9III-V_&lt；lambda&gt；II DS编码的抗体编码。在经常表达LC_4抗原的癌症患者中，Lambda&GT；II DS基因主要用于编码针对LC_4抗原的抗体，而在非癌症患者中，这些基因被自由使用来编码各种针对除LC_4抗原以外的各种外源抗原的抗体。较少

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