CHIMERIZATION OF MU-9 - A COLON-SPECIFIC ANTIGEN-P ANTIBODY-REACTIVE WITH GASTROINTESTINAL CARCINOMAS

BACKGROUND. Mu-9 is a murine monoclonal antibody that is directed agai nst affinity-purified colon-specific antigen-p (CSAp). CSAp is a tumor -associated antigen that is present in 60% of colorectal carcinomas. P reclinical and clinical studies have shown Mu-9 to have excellent targ eting abilities. However, as administration of the murine immunoglobul in G (IgG) provoked a human anti-mouse antibody response, chimerizatio n of Mu-9 is warranted for decreasing immunogenicity. METHODS, Polymer ase chain reaction and cDNA library screening methods were used for th e cloning of Mu-9 heavy and light chain variable regions for the const ruction of chimeric Mu-9. RESULTS, The functional chimeric Mu-9 antibo dy binds to the CSAp antigen in the GW-39 extracts. It has immunochemi cal properties similar to that of murine Mu-9. CONCLUSIONS, The V-regi on sequence information will be used for design of humanized Mu-9, whi ch will be evaluated for targeting gastrointestinal carcinomas. (C) 19 97 American Cancer Society.