MONOCLONAL ANTIBODIES DEFINE CARCINOMA ASSOCIATED AND DIFFERENTIATION ANTIGENS

这些研究包括产生，特征，和 针对抗原的单抗的利用 与人类癌症有关。这些单抗被用来更好地 了解几种人类癌症的细胞生物学和发病机制 并提供可能在以下几个领域有用的试剂 人类癌症的管理。这些方法包括通过 血清检测和/或免疫组织病理学、活体诊断，如伽马 扫描，以及潜在的治疗。产生的单抗可以被分类 根据检测到的抗原的表达分为三组。 这些是：(A)在人类癌症和非癌组织中差异表达的抗原 正常成人组织，如与泛癌相关的肿瘤 单抗B72.3和CC49检测到的糖蛋白(TAG)-72，以及 用Col-1单抗检测的癌胚抗原 COL-15；(B)组织相关抗原，如乳房相关抗原 用单抗DF3检测到的抗原，用DF3检测到的结肠相关抗原 单抗D612；和(C)癌基因或逆转录病毒相关基因产物。 由于已经证明单抗B72.3选择性地针对一系列 癌症的临床试验涉及1000多名患者，研究是 对一系列“第二代”单抗进行了描述 TAG-72抗原。这些研究表明，其中一些第二种 CC83和CC49等世代CC单抗具有更高的亲和力 TAG-72的常量，而不是B72.3，可能更适合B72.3 一些临床应用。TAG-72的血清学图谱已经被 由19个抗TAG-72单抗构建。还进行了一些研究 在CC单抗、COL单抗和单抗D612的分析中 单抗最适合体内临床应用。重点是 也被放在定义和表征与肿瘤相关的 这些单抗检测到的抗原。 以前在项目编号Zoi CB 05233和Z01下报告的工作 CB 09026已纳入该项目。

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 three 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-15; (b) tissue-associated antigens, such as the breast associated antigen detected by MAb DF3, and the colon-associated antigen detected by MAb D612; and (c) oncogene- or retroviral-related gene products. 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 that B72.3 for some clinical applications. A serologic map of TAG-72 has been constructed with 19 anti-TAG-72 MAbs. Studies have also been conducted in the analysis of the CC MAbs, COL MAbs, and MAb D612 to define which MAbs are best suited for in vivo clinical applications. Emphasis has also been placed on defining and characterizing the tumor associated antigens detected by these MAbs. Work previously reported under project numbers ZOI CB 05233 and Z01 CB 09026 have been incorporated into this project.