MONOCLONAL ANTIBODIES DEFINE CARCINOMA ASSOCIATED AND DIFFERENTIATION ANTIGENS

这些研究包括产生、表征和利用 针对相关抗原的单抗(MAb) 人类癌症。这些单抗被用来更好地了解细胞 几种人类癌症的生物学和发病机制并提供 在人类管理的几个领域中可能有用的试剂 癌症。这包括通过血清检测和/或体外诊断 免疫组织病理学，活体诊断，如伽马扫描，以及 潜在的治疗方法。到目前为止产生的单抗可以分类为 根据检测到的抗原的表达情况分为三组。这些是 (A)人类肿瘤与正常组织中差异表达的抗原 成人组织，如胰腺癌肿瘤相关糖蛋白 (Tag)-72，由单抗B72.3检测，以及癌胚抗原(CEA) 其由单抗Col-1至Col-15检测；(B)组织相关 抗原，如单抗DF3检测到的乳房相关抗原，以及 用单抗D612和CAA检测到的结肠相关抗原；和(C) 癌基因或逆转录病毒相关基因产物，如int-2。 由于单抗B72.3已被证明可以选择性地靶向一系列癌症 在涉及数百名患者的临床试验中，研究 致力于将一系列“第二代”单抗定性为 TAG-72抗原。初步研究表明，其中一些第二种 世代CC单抗，如CC83和CC49，具有较高的亲和力常数 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的血清学图谱已经用 19株抗TAG-72株单抗。还进行了研究，以分析 COL单抗系列和单抗D612，用于定义哪些单抗最适合 活体临床应用。主要的重点是 TAG-72重组/嵌合(REC/CHI)单抗的制备与分析 和抗CEA单抗和D612以及这些rec/chi的修饰结构 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。

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.