Molinolo A, Simpson J F, Thor A, Schlom J
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892.
Cancer Res. 1990 Feb 15;50(4):1291-8.
Monoclonal antibody (MAb) B72.3 was generated using a membrane-enriched fraction of a human mammary carcinoma biopsy. It has demonstrated reactivity to the majority of human adenocarcinomas including colorectal, gastric, pancreatic, ovarian, endometrial, mammary, and nonsmall cell lung cancer as well as weak or nondetectable reactivity to the majority of normal adult tissues, with the exception of secretory endometrium. Radiolabeled B72.3 has demonstrated MAb localization of carcinoma in approximately 70% of several hundred colorectal and ovarian carcinoma patients. The B72.3-reactive antigen, tumor-associated glycoprotein 72, has been purified from a human colon cancer xenograft and used as an immunogen to generate second generation MAbs. Twenty-eight of these MAbs, designated CC (colon cancer), were shown to be reactive with tumor-associated glycoprotein 72; direct-binding radioimmunoassays, Western blotting, live cell surface binding assays, liquid competition radioimmunoassays, and affinity constant measurements distinguished CC MAbs from each other and from B72.3. Two of these MAbs, CC49 and CC112, were selected for further immunohistochemical characterization. These MAbs were tested here against a spectrum of normal, benign, and malignant human adult tissues using the avidin-biotin-peroxidase technique, and their reactivity was compared with B72.3. Both CC MAbs were more reactive than B72.3 against a range of tumors. Extensive testing with MAbs CC49 and B72.3 using serial tissue sections demonstrated that both MAbs reacted similarly to most normal adult tissues with MAb CC49 reacting stronger to inflammatory colonic tissue. In 35 of 48 (72%) carcinoma biopsies of the gastrointestinal tract, ovary, breast, and lung in which one of the MAbs reacted to at least 20% of the cells, CC49 reacted to a greater percentage of carcinoma cells and/or tumor-associated mucin than B72.3. The reciprocal was observed in only 2% of the carcinomas. This study thus provides evidence that these second generation anti-tumor-associated glycoprotein MAbs may be more efficient than B72.3 in the further study of human carcinoma cell populations and in the diagnostic and therapeutic procedures presently being pursued with MAb B72.3.
单克隆抗体（MAb）B72.3是利用人乳腺癌活检组织的富含膜成分制备的。它已显示出对大多数人类腺癌有反应性，包括结直肠癌、胃癌、胰腺癌、卵巢癌、子宫内膜癌、乳腺癌和非小细胞肺癌，而对大多数正常成人组织反应较弱或检测不到，但分泌期子宫内膜除外。放射性标记的B72.3在数百名结直肠癌和卵巢癌患者中约70%显示出癌的单克隆抗体定位。B72.3反应性抗原，即肿瘤相关糖蛋白72，已从人结肠癌异种移植瘤中纯化出来，并用作免疫原以产生第二代单克隆抗体。这些单克隆抗体中有28种，命名为CC（结肠癌），显示与肿瘤相关糖蛋白72有反应性；直接结合放射免疫测定、蛋白质印迹、活细胞表面结合测定、液相竞争放射免疫测定和亲和常数测量将CC单克隆抗体彼此区分开来，并与B72.3区分开来。其中两种单克隆抗体，CC49和CC112，被选用于进一步的免疫组织化学特征分析。使用抗生物素蛋白-生物素-过氧化物酶技术，将这些单克隆抗体针对一系列正常、良性和恶性人类成人组织进行检测，并将它们的反应性与B72.3进行比较。两种CC单克隆抗体在一系列肿瘤上的反应性均比B72.3更强。使用连续组织切片对单克隆抗体CC49和B72.3进行的广泛检测表明，两种单克隆抗体对大多数正常成人组织的反应相似，其中单克隆抗体CC49对炎症性结肠组织的反应更强。在48例胃肠道、卵巢、乳腺和肺部癌活检组织中，有35例（72%）中其中一种单克隆抗体对至少20%的细胞有反应，CC49对癌细胞和/或肿瘤相关粘蛋白的反应百分比高于B72.3。在仅2%的癌组织中观察到相反情况。因此，本研究提供了证据，表明这些第二代抗肿瘤相关糖蛋白单克隆抗体在进一步研究人类癌细胞群体以及目前使用单克隆抗体B72.3进行的诊断和治疗程序中可能比B72.3更有效。
