Reactivity of a human monoclonal antibody against carcinomas and other lesions of the colon.
Reactivity of a human monoclonal antibody against carcinomas and other lesions of the colon.
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人单克隆抗体对结肠癌和其他病变的反应性。
DOI：
10.1007/bf00205240
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Kan-Mitchell,J
中科院分区：
文献类型：
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作者：
Formenti,SC;Mitchell,MS;Taylor,CR;Lipkin,M;Jernstrom,PH;Kan-Mitchell,J
为了鉴定可能对人具有免疫原性的肿瘤相关抗原，通过将非分泌性小鼠骨髓瘤细胞与来自结肠腺癌患者区域肠系膜淋巴结的淋巴细胞融合来产生人单克隆抗体（人mAb）。通过其对人肿瘤异种移植物的反应性鉴定了一种IgG1人mAb，命名为14 - 31 - 10。我们研究了mAb 14 - 31 - 10与福尔马林固定、石蜡包埋的人结肠标本的反应性。共86例进行了研究，包括正常成人和胎儿结肠，结肠腺癌，和各种结肠炎性疾病和癌前病变。18例结肠腺癌中有15例呈强阳性反应，而10例正常成人和4例胎儿结肠粘膜均呈阴性反应。有趣的是，在4例癌中，在组织学正常粘膜中也观察到反应性，位于原发性病变10 cm或以上。另一方面，在16个炎性病变中均未检测到染色。在38个癌前病变中，仅6个显示mAb染色：5个良性管状腺瘤性息肉中的1个，9个绒毛状腺瘤和管状绒毛状息肉中的3个，5个溃疡性结肠炎标本中的1个和19个家族性息肉病标本中的1个。然而，在这些病例中，染色强度仅为中度。因此，我们的数据表明，由人单克隆抗体14 - 31 - 10鉴定的表位在结肠的癌前病变和肿瘤病变中以及在与原发性结肠癌有一定距离的表面上正常的粘膜中显示出优先表达。在所有情况下，染色均为细胞质，表明靶抗原位于细胞质或内膜位置。这种抗原似乎不同于癌胚抗原，因为在相同标本的连续切片中，14 - 31 - 10的染色与癌胚抗原的小鼠单克隆抗体的染色始终不同。14 - 31 - 10的有限反应性表明其在免疫组织化学中的潜在应用。此外，由mAb 14 - 31 - 10鉴定的表位可在正常粘膜向瘤形成的进展期间表达。
To identify tumor-associated antigens that may be immunogenic to man, human monoclonal antibodies (human mAb) were generated by fusing nonsecreting mouse myeloma cells with lymphocytes from regional mesenteric nodes of patients with adenocarcinomas of the colon. One IgG1 human mAb, designated as 14-31-10, was identified by its reactivity against human tumor xenografts. We have studied the reactivity of mAb 14-31-10 with formalin-fixed, paraffin-embedded specimens of human colon. A total of 86 cases were studied, including normal adult and fetal colons, adenocarcinomas of the colon, and a variety of colonic inflammatory diseases and preneoplastic lesions. Intense reactivity was found in 15 of 18 adenocarcinomas of the colon, but not in 10 specimens of normal adult or 4 specimens of fetal colonic mucosa. Interestingly, in four cases of carcinoma, reactivity was also observed in histologically normal mucosa situated 10 cm or more from the primary lesion. On the other hand, no staining was detected in any of the 16 inflammatory lesions. Of the 38 preneoplastic lesions, only 6 showed staining by the mAb: 1 of 5 benign tubular adenomatous polyps, 3 of 9 villous adenomas and tubovillous polyps, 1 of 5 specimens of ulcerative colitis and 1 of 19 specimens of familial polyposis. However, the intensity of staining was only moderate in those cases. Our data, therefore, suggest that the epitope identified by the human mAb 14-31-10 shows preferential expression in preneoplastic and neoplastic lesions of the colon, and in ostensibly normal mucosa at some distance from a primary colonic carcinoma. In all instances, the staining was cytoplasmic, suggesting a cytoplasmic or internal membrane location of the target antigen. This antigen appeared to be distinct from carcinoembryonic antigen, since staining by 14-31-10 was consistently different from that of a mouse monoclonal antibody to carcinoembryonic antigen in serial sections of the same specimens. The restricted reactivity of 14-31-10 suggests its potential application in immunohistochemistry. Moreover, the epitope identified by mAb 14-31-10 may be expressed during the progression of normal mucosa to neoplasia.