Our research effort is aimed at designing and constructing recombinant immunoglobulin genes derived from hybridomas releasing monoclonal antibodies (MAbs) against human tumor-associated antigens. The purpose of this effort is to modify the MAbs to: 1) reduce their immunogenicity in patients, 2) enhance the pharmacokinetics of the MAbs in patients, and 3) increase the binding of the MAb for the target antige, We have obtained recombinant clones of genomic DNA containing the rearranged vari- able regions of the heavy and light chain genes from the 72.3 hybridoma. The nucleotide sequence of the light chain gene has been determined. In addition, the IgKVJ sequences have been inserted into an expression vector containing human Ig constant region. Cells transfected with this vector express human-mouse chimeric 72.3 Ig. Similar experiments are underway with the 72.3 Ig VDJ-containing recombinant clone.
