Characterization and Selection Criteria of Monoclonal Antibodies for Tumor Imaging Studies
Evidence now exists that abnormalities of cell-surface molecular architecture are often associated with cancer. These subtle, yet dramatic changes, are the result of alterations in the gene regulation mechanism leading to either a blockage, stimulation or neosynthesis of cell surface molecules which, under normal conditions, would mediate cell-cell interaction and cellular differentiation (1,2). Thus, cells which have been oncologically transformed either in vitro or in vivo, will display sufficiently different profiles from their progenitor cells that they can be targeted by means of monoclonal antibodies (MAbs) which in turn could carry a number of cytotoxic agents or radionuclides. On the surface, this approach appears to be not only elegant but rather simple. In actual fact, the problems encountered in the design of such probes are predicated by the availability of the right MAb which recognizes not only a particularly well-defined chemical structure, but also an epitope of such structure consistent with the cell membrane environment of the tumor cell. Even if such a “magic bullet” were to be found, other dynamic characteristics of cell membrane constituents alter, to an extent, the degree of specificity of the selected MAb. While fundamental questions are often raised as to the importance of marker turnover as a function of cell differentiation, others are related to the relevance of the animal models so often used prior to immunoscintigraphic studies. Such diversities frequently pose considerable difficulties when selecting the appropriate antibody for clinical trials. An excellent review of this subject has been presented by Larson (3). In our laboratory, we have been interested in generating MAbs against cancer-associated carbohydrate markers and the use of such MAbs for the in vivo and in vitro detection of human tumors (4,5). Some of our experience in selecting and characterizing these MAbs is described in this paper.
KeywordsAmmonium Sulfate Protein Recovery Detergent Extract Free Sulfhydryl Group Bifunctional Chelate
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