CHARACTERIZATION OF HUMAN OVARIAN CARCINOMA-ASSOCIATED ANTIGENS DEFINED BY NOVEL MONOCLONAL-ANTIBODIES WITH TUMOR-RESTRICTED SPECIFICITY
CHARACTERIZATION OF HUMAN OVARIAN CARCINOMA-ASSOCIATED ANTIGENS DEFINED BY NOVEL MONOCLONAL-ANTIBODIES WITH TUMOR-RESTRICTED SPECIFICITY
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DOI：
10.1002/ijc.2910390306
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发表时间：
1987-03-15
影响因子：
6.4
通讯作者：
COLNAGHI, MI
中科院分区：
文献类型：
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作者：
MIOTTI, S;CANEVARI, S;COLNAGHI, MI
本文报道了三株新的抗人卵巢癌单克隆抗体（MOv 16、MOv 18和MOv 19）。为了获得比迄今为止生产的试剂更特异的试剂，我们采用了以下实验方法，包括：（1）选择与我们实验室先前选择的所有单克隆抗体均不反应的低分化卵巢癌;（2）应用特定的免疫方案。通过固相RIA对来自肿瘤细胞系的活细胞和固定细胞以及通过对来自手术标本的冷冻切片的免疫荧光来研究所选择的单克隆抗体的反应性。MAb MOv 16与60%的卵巢癌以及高比例的其他癌和一些正常组织反应。相比之下，MOv 18和MOv 19似乎对卵巢癌和囊腺瘤具有有限的特异性。仅在少数病例中观察到对其他癌的反应性，在非上皮性肿瘤或正常组织中未发现反应性。免疫沉淀实验表明MOv 16识别48-50-kDA蛋白，而MOv 18和MOv 19都识别38-40 kDA糖蛋白带。交叉竞争实验，连同使用MOv 18作为捕捉器和MOv 19作为示踪剂的双决定簇免疫放射测定，表明它们识别由相同分子携带的不同表位。MOv 18和MOv 19的亲和常数估计在108-109 M-1的范围内。两者合计，这些抗体的性质，其限制卵巢肿瘤特异性和相对高的亲和力常数，表明它们可以代表有前途的工具，在体内应用。
Three new monoclonal antibodies (MAbs) (MOv16, MOv18 and MOv19) were raised against human ovarian carcinoma. To obtain more specific reagents than those produced so far, we adopted the following experimental approach which consisted of: (1) the selection of a poorly differentiated ovarian carcinoma which was unreactive with all the MAb previously selected in our laboratory; and (2) the application of a particular immunization protocol. The reactivity of the selected MAbs was studied by solid-phase RIA on live and fixed cells from tumor cell lines and by immunofluorescence on frozen sections from surgical specimens. The MAb MOv16 reacted with 60% of ovarian carcinomas as well as with a high percentage of other carcinomas and with some normal tissues. In contrast, MOv18 and MOv19 appeared to have restricted specificities for ovarian carcinomas and cystadenomas. Reactivity on other carcinomas was only observed in a few cases and no reactivity was found on non-epithelial tumors or normal tissues. Immunoprecipitation experiments indicated that MOv16 recognizes a 48-50-kDA protein, whereas MOv18 and MOv19 both identify a 38-40 kDA glycoprotein band. Cross-competition experiments, together with a double-determinant immunoradiometric assay which uses MOv18 as catcher and MOv19 as tracer, suggested that they recognize different epitopes carried by the same molecule. The affinity constants of MOv18 and MOv19 were estimated to be in the range of 108-109 M-1. Taken together, the properties of these antibodies, their restricted ovarian tumor specificities and relative high affinity constants, suggest that they could represent promising tools for in vivo applications.