Goldstein N I, Nagle R, Villar H, Hersh E, Fisher P B
ImClone Systems, Inc., New York, New York 10014.
Anticancer Res. 1990 Nov-Dec;10(6):1491-500.
A human monoclonal antibody with specificity for breast and colorectal carcinoma has been isolated after hybridoma formation between regional lymph node lymphocytes from a patient with breast carcinoma and a mouse x human heteromyeloma (SPAZ-4). The monoclonal, MAB 15.2.3, is an IgM, kappa, which binds to an epitope found on at least four glycoproteins with approximate molecular weights of 37, 39, 43 and 56 kilodaltons (kD). These antigens are expressed intracellularly and on the surface of breast and colorectal carcinoma cells and their level of expression is increased by treatment with recombinant human leukocyte (IFN-alpha A) or immune (IFN-gamma) interferon. Analysis of formalin-fixed tumor cell lines indicates specificity for carcinomas. Similarly, immunostaining of paraffin-embedded tissue indicates both cell membrane and intracytoplasmic reactivity with breast (8 of 12), colorectal (3 of 4) and prostate (1 of 3) carcinomas. By employing a series of enzymes which specifically cleave sugar residues on proteins, it was demonstrated that the binding of MAB 15.2.3 could be increased. These observations suggest that the epitope recognized by MAB 15.2.3. is protein in nature and expressed on a series of glycoproteins. Pretreatment of Colo 205 (human colorectal carcinoma) cells with MAB 15.2.3 prior to implantation into nude mice, results in a reduction in the size and weight of tumors. With appropriate genetic engineering, resulting in the conversion of this antibody to an IgG, MAB 15.2.3. could prove of value for the diagnosis and ultimately the therapy of human breast and colorectal carcinomas.
从一名乳腺癌患者的区域淋巴结淋巴细胞与小鼠 - 人杂种骨髓瘤（SPAZ - 4）形成杂交瘤后，分离出了一种对乳腺癌和结直肠癌具有特异性的人单克隆抗体。该单克隆抗体MAB 15.2.3是一种IgM、κ型抗体，它能与至少四种糖蛋白上发现的一个表位结合，这些糖蛋白的分子量约为37、39、43和56千道尔顿（kD）。这些抗原在乳腺癌和结直肠癌细胞的细胞内及表面表达，用重组人白细胞（IFN - αA）或免疫（IFN - γ）干扰素处理后其表达水平会升高。对福尔马林固定的肿瘤细胞系分析表明该抗体对癌具有特异性。同样，对石蜡包埋组织的免疫染色显示，该抗体与乳腺癌（12例中的8例）、结直肠癌（4例中的3例）和前列腺癌（3例中的1例）的细胞膜及胞浆均有反应。通过使用一系列能特异性切割蛋白质上糖残基的酶，证明MAB 15.2.3的结合能力可以增强。这些观察结果表明，MAB 15.2.3识别的表位本质上是蛋白质，且在一系列糖蛋白上表达。将Colo 205（人结直肠癌细胞）细胞在植入裸鼠前用MAB 15.2.3预处理，可使肿瘤的大小和重量减小。通过适当的基因工程，将该抗体转化为IgG后，MAB 15.2.3可能对人类乳腺癌和结直肠癌的诊断乃至治疗具有价值。
