MONOCLONAL ANTIBODIES DEFINE CARCINOMA ASSOCIATED AND DIFFERENTIATION ANTIGENS

单克隆抗体定义癌相关抗原和分化抗原

• 批准号: 3813325
• 负责人: J SCHLOM
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813325
• 关键词: antibody formation; antibody specificity; antitumor antibody; breast neoplasms; carcinoembryonal antigen; carcinoma; cell differentiation; cellular oncology; colon neoplasms; genetic manipulation; glycoproteins; human tissue; hybrid antibody; hybridomas; immunoglobulins; laboratory mouse; metastasis; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; oncogenes; oncoproteins; pancreas neoplasms; tumor antigens

These studies involve the generation, characterization, and utilization of monoclonal antibodies (MAbs) directed against antigens associated with human carcinoma. 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 thus far 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 MAb B72.3, 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 antigens detected by MAbs D612 and CAA; and (c) oncogene- or retroviral-related gene products, such as int-2. Since MAb B72.3 has been shown to selectively target a range of carcinomas in clinical trials involving several hundred patients, studies were undertaken to characterize a series of "second generation" MAbs to the TAG-72 antigen. Initial studies indicate 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. 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 COL MAb series and MAb D612 to define which MAbs are best suited for in vivo clinical applications. Major emphasis is being placed on the generation and analysis of recombinant/chimeric (rec/chi) MAbs to TAG-72 and anti-CEA MAbs and D612 and modified constructs of these rec/chi immunoglobulins. These rec/chi constructs and modified forms may be better suited for diagnostic and therapeutic applications.

这些研究涉及的生成，表征和利用 针对与以下相关的抗原的单克隆抗体（MAb） 人类癌这些单克隆抗体被用来更好地了解细胞 生物学和发病机制，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。迄今为止产生的MAb可分为 基于检测到的抗原的表达分为三组。这些是 (a)在人癌与正常人中差异表达的抗原 成人组织，如泛癌肿瘤相关糖蛋白 （TAG）-72（通过MAb B72.3检测）和癌胚抗原（CEA） 其由MAb COL-1至COL-15检测;（B）组织相关的 抗原，如通过MAb DF 3检测的乳房相关抗原，和 通过MAb D 612和CAA检测的结肠相关抗原;和（c） 致癌基因或逆转录病毒相关基因产物，如int-2。 由于单克隆抗体B72.3已显示出选择性靶向一系列癌， 在涉及数百名患者的临床试验中， 进行表征一系列“第二代”单克隆抗体， TAG-72抗原初步研究表明，其中一些第二次 第二代CC单抗，如CC 83和CC 49，具有较高的亲和常数 对于TAG-72，比B72.3更适合，对于某些情况，可能比B72.3更适合 临床应用。TAG-72的血清学图谱已用 19种抗TAG-72单克隆抗体。还进行了研究，分析 COL MAb系列和MAb D 612，以确定哪种MAb最适合于 体内临床应用。主要重点是 TAG-72的重组/嵌合（rec/chi）MAb的产生和分析 和抗CEA MAb和D 612以及这些rec-chi的修饰的构建体 免疫球蛋白。这些rec/chi结构和修改后的形式可能更好 适用于诊断和治疗应用。