CHARACTERIZATION OF MONOCLONAL-ANTIBODY PAM4 REACTIVE WITH A PANCREATIC-CANCER MUCIN
CHARACTERIZATION OF MONOCLONAL-ANTIBODY PAM4 REACTIVE WITH A PANCREATIC-CANCER MUCIN
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DOI：
10.1002/ijc.2910570213
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发表时间：
1994-04-15
影响因子：
6.4
通讯作者：
CARDILLO, T
中科院分区：
文献类型：
--
作者：
GOLD, DV;LEW, K;CARDILLO, T
一种单克隆抗体（MAb）， PAM4，对胰腺癌具有反应性。PAM4是一种IgG(1)免疫球蛋白，用从移植的RIP I型人胰腺癌中纯化的粘蛋白免疫小鼠产生。正常成人组织的免疫组织化学研究显示PAM4反应性表位仅限于胃肠道，而在正常胰腺中不存在。在肿瘤组织中，85%的胰腺癌、大约一半的结肠癌、乳腺癌、卵巢癌、前列腺癌、肾癌和肝癌均无PAM4反应。PAM4一般对胰腺炎标本无反应，而CA19.9和DUPAN2对两者均有强烈反应。通过加热、减少二硫键或蛋白酶消化来处理粘蛋白抗原，可以消除PAM4的免疫反应性。用神经氨酸酶或高碘酸盐氧化处理黏蛋白可降低免疫反应性，但不能完全消除。我们的数据与PAM4表位是构象依赖性肽表位的建议一致，并且某些碳水化合物结构是维持正确肽构象所必需的。PAM4对胰腺癌组织的高特异性和强反应性表明，该抗体可用于体外诊断分析以及诊断和治疗药物的体内靶向。(C) 1994 Wiley-Liss, Inc。
A monoclonal antibody (MAb), PAM4, having reactivity with pancreatic carcinoma has been developed. PAM4 is an IgG(1) immunoglobulin produced by immunization of mice with mucin purified from the xenografted RIP I human pancreatic carcinoma. An immunohistochemical study of normal adult tissues showed the PAM4 reactive epitope to be restricted to the gastrointestinal tract and absent from normal pancreas. In neoplastic tissue, PAM4 was reactive with 85% of the pancreatic carcinomas, approximately half of the colon cancers and none of the breast, ovarian, prostate, renal and liver cancers. PAM4 was, in general, non-reactive with pancreatitis specimens whereas CA19.9 and DUPAN2 were strongly reactive with each one. Treatment of the mucin antigen by heating, reduction of disulfide bonds, or protease digestion abolished immunoreactivity with PAM4. Treatment of the mucin by neuraminidase or periodate oxidation reduced immunoreactivity but did not completely abolish it. Our data are consistent with the proposal that the PAM4 epitope is a conformationally dependent peptide epitope and that certain carbohydrate structures are necessary in order to maintain the correct peptide conformation. The high specificity and intense reactivity of PAM4 with pancreatic carcinoma tissue suggests that the antibody may prove useful for in vitro diagnostic assays as well as in vivo targeting of diagnostic and therapeutic agents. (C) 1994 Wiley-Liss, Inc.