In the past year, some advances have been made in mimicking in vivo antibody generation by use of molecular biology approaches. The most significant breakthrough was the development of the phage Fab/Fv display library technology. There is interest in exploring the application of this technology to cancer research and antibody engineering. An anti-ETS2 monoclonal antibody T-7 light chain, U-244 heavy chain, and a presumably heavy chain-related sequence from both T-7 and U-244, have been cloned successfully. A new Fab combinatorial library construction strategy for a more diverse repertoire has been designed. Mouse splenic anti-erg Fab cDNAs are to be cloned and screened by this strategy. The phage Fab display vector has been requested from MRC. An anti-erg Fab display library will be made to verify the efficiency of the system. Some BALB/c mice have been immunized with several clinical tumor samples and their normal controls. Fab display libraries will be made, and those anti-tumor marker clones will be selected by panning or affinity chromatography. For high-affinity Fab, a new approach to generate random mutagenesis to desired domains has been started and this work will continue. An approach to generate a new generation of therapeutic monoclonal antibodies by combining desired specificity associated with antibody variable domains with the defined antibody effector function associated with some monoclonal antibody constant domains has been designed. Several monoclonal antibody cell lines are to be characterized.
