CONSTRUCTION OF A CHIMERIC ANTIBODY WITH THERAPEUTIC POTENTIAL FOR CANCERS WHICH OVEREXPRESS C-ERBB-2

We describe the chimerization of a monoclonal antibody directed agains t the c-erbB-2 protein using a novel PCR method for cloning immunoglob ulin variable region genes. We also describe the characterization of t he chimera and show its potential use for treating cancers which overe xpress the c-erbB-2 protein. The genomic DNA fragments of heavy and li ght chain variable genes were cloned by PCR using uniquely designed pr imers which allowed for isolation of genes containing functional promo ters, signal and coding sequences. The chimeric genes were then constr ucted by linking variable regions of murine genes to human constant ga mma 1 and kappa genes. Expression of the chimeric immunoglobulin genes resulted in production of properly assembled chimeric antibody with i mproved biological properties. (C) 1995 Academic Press, Inc.