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.
