Gross N, Beck D, Portoukalian J, Favre S, Carrel S
Department of Pediatrics, CHUV, Lausanne, Switzerland.
Int J Cancer. 1989 Apr 15;43(4):665-71. doi: 10.1002/ijc.2910430421.
Three monoclonal antibodies (IgG2) have been produced from hybridomas obtained by fusion of murine myeloma cells and spleen cells of mice hyperimmunized with gamma-interferon-treated neuroblastoma cells. The 3 MAbs, 7A4, 2A6 and IG8, detected an antigen present on neuroblastoma tumors and cell lines, but also on some neuro-ectoderm-derived tissues and cells. All 3 clones were shown to react with an epitope of the di-sialo-ganglioside GD2 molecules highly expressed by some neuro-ectoderm-derived tumors, mainly neuroblastoma. Whereas MAb IG8 specificity was restricted to GD2 and its o-acylated form, MAb 2A6 and 7A4 were also able to detect GD3 at high concentration of antibody as shown by TLC analysis and immunodetection. The 3 MAbs were able to lyse 100% neuroblastoma cells in the presence of rabbit or human complement. Direct binding assays with 125I-labelled MAbs showed that MAb 7A4 might be a good candidate for in vivo immunolocalization experiments. The high proportion of anti-GD2 MAbs obtained by our fusion and the increased binding of anti-GD2 MAbs on gamma-IFN-treated neuroblastoma cells suggests a modulation of the exposure and an increase in the immunogenicity of GD2 induced by gamma-IFN.
通过将鼠骨髓瘤细胞与用γ干扰素处理的神经母细胞瘤细胞超免疫的小鼠脾细胞融合获得的杂交瘤产生了三种单克隆抗体（IgG2）。这三种单克隆抗体7A4、2A6和IG8检测到一种存在于神经母细胞瘤肿瘤和细胞系上的抗原，也存在于一些神经外胚层衍生的组织和细胞上。所有这三个克隆都显示与一些神经外胚层衍生肿瘤（主要是神经母细胞瘤）高度表达的二唾液酸神经节苷脂GD2分子的一个表位发生反应。虽然单克隆抗体IG8的特异性仅限于GD2及其O-酰化形式，但薄层层析分析和免疫检测表明，在高抗体浓度下单克隆抗体2A6和7A4也能够检测到GD3。在存在兔或人补体的情况下，这三种单克隆抗体能够裂解100%的神经母细胞瘤细胞。用125I标记的单克隆抗体进行的直接结合试验表明，单克隆抗体7A4可能是体内免疫定位实验的一个良好候选者。我们通过融合获得的抗GD2单克隆抗体的高比例以及抗GD2单克隆抗体在γ干扰素处理的神经母细胞瘤细胞上结合的增加表明，γ干扰素诱导了GD2暴露的调节和免疫原性的增加。
