The use of mouse-human chimeric (engineered) monoclonal antibodies could prevent the immune response which murine monoclonal antibodies elicit when injected into humans for therapeutic or diagnostic uses. The purpose of this research project is to evaluate by immunohistochemical methods the reactivity of engineered monoclonal antibodies in normal tissues and neoplasms from patients who are candidates for imaging procedures and immunotherapy with such antibodies and in patients who have been imaged preoperatively with such antibodies. The general immunoreactivity of the newly engineered antibodies will be compared with that of the original antibody against a large panel of normal tissues and neoplasms from our frozen tumor bank as well as utilizing multi-tumor blocks prepared with paraffin embedded tissues with a variety of fixatives. Standard immunohistochemical methods will be employed together with modifications made necessary because of the changed configuration of the antibody molecule. Quantification of the mophometric data by computerized image analysis techniques will be performed in order to correlate the in vivo localization of the tumor as determined by results of imaging and biodistribution studies performed by other investigators involved in the research program. Studies regarding antigenic expression, heterogeneity, and modulation of tumor cells will be performed by Flow Cytometric analysis using single cell suspensions obtained from human colon tumor xenografts in athymic mice from biodistribution/therapy studies and human colorectal carcinomas from diagnostic clinical trials. Correlations between parameters that could alter the antigenic expression in tumors such as cell cycle and previous exposure to monoclonal antibodies will be accomplished. Applying similar methods in addition to autoradiography and immunoelectronmicroscopy, we will search for the antigenic sites at the ultrastructural level in liver cells, information which may be valuable to monitor attempts at minimizing the liver uptake.
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