MONOCLONAL ANTIBODIES DEFINE CARCINOMA ASSOCIATED AND DIFFERENTIATION ANTIGENS

这些研究涉及的产生，表征，和利用 单克隆抗体（MAb）针对与 人类癌 这些单克隆抗体被用来更好地了解 细胞生物学和几种人类癌症的发病机制，并提供 本发明涉及可用于人类免疫缺陷管理的若干领域的试剂， carcinoma. 这些方法包括通过血清测定和/或 免疫组织病理学、体内诊断如γ扫描，和 潜在的治疗。 产生的单克隆抗体可分为两类 基于检测到的抗原的表达进行分组。 这是（a） 在人癌与正常成人中差异表达的抗原 组织，如泛癌肿瘤相关糖蛋白（TAG）-72 用单克隆抗体B72.3和CC 49及癌胚抗原检测 (CEA)其由MAb COL-1至COL-1 5检测;或（B） 组织相关抗原，如检测到的结肠相关抗原 MAb D612 由于MAb B72.3已显示选择性靶向一系列的 在涉及1000多名患者的临床试验中， 进行了一系列“第二代”单克隆抗体的表征， TAG-72抗原 这些研究表明，其中一些第二 第二代CC单抗，如CC 83和CC 49，具有更高的亲和力， TAG-72比B72.3更稳定，可能比B72.3更适合于 一些临床应用。 260例结直肠癌患者血清中TAG-72的检测 已经使用CA 72 -4测定来评估疾病（恶性或良性）。 大约40%的结直肠癌患者表现出 此外，该标记物的水平， TAG-72与疾病的晚期显著相关。 这些 研究表明，TAG-72和CEA血清标志物的同时使用 可能有助于诊断复发性疾病，因此 在癌症患者的临床管理中发挥作用。

These studies involve the generation, characterization, and utilization of monoclonal antibodies (MAbs) directed against antigens associated with human carcinomas. These MAbs are being used to better understand the cell biology and pathogenesis of several human carcinomas and to provide reagents that may be useful in several areas of the management of human carcinoma. These include in vitro diagnosis via serum assays and/or immunohistopathology, in vivo diagnosis such as gamma scanning, and potentially therapy. The MAbs generated can be classified into two groups based on the expression of the detected antigens. These are (a) antigens differentially expressed in human carcinoma versus normal adult tissues, such as the pancarcinoma tumor-associated glycoprotein (TAG)-72 which is detected by MAbs B72.3 and CC49, and carcinoembryonic antigen (CEA) which is detected by MAbs COL-1 through COL-1 5; or (b) tissue-associated antigens, such as the colon-associated antigen detected by MAb D612. Since MAb B72.3 has been shown to selectively target a range of carcinomas in clinical trials involving over 1000 patients, studies were conducted to characterize a series of 'second generation' MAbs to the TAG-72 antigen. These studies demonstrated that some of these second generation CC MAbs, such as CC83 and CC49, have a higher affinity constant for TAG-72 than B72.3, and may be better suited than B72.3 for some clinical applications. The presence of TAG-72 in serum samples from 260 patients with colorectal disease (malignant or benign) has been evaluated using the CA72-4 assay. Approximately 40% of patients with colorectal cancer exhibit elevated levels of this marker, moreover, the presence of positive levels of TAG-72 significantly correlates with advanced stages of disease. These studies suggest that the simultaneous use of TAG-72 and CEA serum markers may be useful in the diagnosis of recurrent disease and may therefore play a role in the clinical management of cancer patients.