HIGH BINDING-AFFINITY CHIMERIC ANTI-COLORECTAL CARCINOMA ANTIBODY CORRELATED TO ENHANCED TUMOR BINDING AND EFFECTOR FUNCTION

The genetically engineered mouse/human chimeric cB72.3m4 and cB72.3m12 antibodies all recognized the tumor-associated TAG72 antigen. The hig h affinity cB72.3m4 antibody had an approximately 18-fold higher affin ity constant for the TAG72 antigen than the low affinity cB72.3m12 ant ibody. The relationship amongst antibody binding affinity, tumor bindi ng and effector functions was studied by using these two antibodies. T he data showed that the high affinity cB72.3m4 antibody was reactive w ith, on average, 15% more colon adenocarcinoma cells on tissue section s than the low affinity cB72.3m12 antibody, and it did not produce any cross-reactivities with various normal tissues. The high affinity cB7 2.3m4 antibody was able to mediate more effective ADCC and CDC to the human ovarian cancer cells in vitro than the low affinity cB72.3m12 an tibody. This study provides evidence that this high affinity chimeric cB72.3m4 antibody may be useful in both immunodetection and immunother apy of cancer.