BIOLOGICAL-ACTIVITY OF 2 HUMANIZED ANTIBODIES AGAINST 2 DIFFERENT BREAST-CANCER ANTIGENS AND COMPARISON TO THEIR ORIGINAL MURINE FORMS

We have humanized two monoclonal antibodies (MoAbs), hu-BrE-3 and hu-M B, that are bound to two different antigens of the breast epithelial c ell, They bind to the breast epithelial mucin (M(r) 400,000) and the B A46 antigen (M(r) 46,000). They could participate in a joint radioimmu notherapy strategy administering repeated or fractionated dosages, whe re increased irradiation could be delivered by their simultaneous admi nistration. Both antibodies, hu-BrE-3 and hu-Mc3, had similar reactivi ty to their antigens and similar binding affinity as those of their or iginal murine forms. However, because humanized MoAbs could have diffe rent pharmacokinetic and radioimmunotherapeutic characteristics than t heir original murine forms, the experimental biodistribution in vivo o f both of these two humanized anti-breast tumor MoAbs was compared to their original murine forms. Biodistributions in immunodeficient mice grafted with transplantable human breast tumors, both after radioiodin ation and In-111 labeling via anatobenzyl-methyl-diethylene-triaminepe nta-acetic acid (MXDTPA), demonstrated comparable tumor:normal tissue ratios for the humanized and murine forms. In radioimmunotherapy, the humanized forms for both MoAbs showed also similar tumoricidal activit y as that of the original murine MoAbs. These results show that the ne w humanized forms are amenable to conjugation and radioisotope labelin g without loss of biological activity. Furthermore, they demonstrate t hat these engineered molecules kept intact, both qualitatively and qua ntitatively, their binding ability, pharmacokinetics, and radioimmunot herapeutic characteristics after the humanization process.