BREAST-TUMOR XENOGRAFT TARGETING AND THERAPY STUDIES USING RADIOLABELED CHIMERIC ANTI-CEA MONOCLONAL-ANTIBODY T84.66

Carcinoembryonic antigen (CEA) is expressed in approximately 60% of br east carcinomas. T84.66 is a well characterized anti-CEA murine monocl onal antibody (MAb) that does not cross-react with other CEA-related p roteins. It has been humanized and used extensively after radiolabelin g in clinical/experimental protocols for localization/therapy of color ectal cancer. MCF-7 human breast cancer cell line expresses CEA and is tumorigenic in athymic mice. In order to determine if anti-CEA MAb co uld specifically target breast cancer CEA, biodistribution, radiolocal ization and therapy studies were performed in the animal model. Five t umor-bearing animals per time point were injected with 15 muCi of In-1 11-cT84.66. Mice were imaged and sacrificed at 24, 48, 72 and 144 h an d biodistribution studies performed. For therapy studies, 19 tumor-bea ring mice were injected either with 120 muCi of 90Y-cT84.66 or PBS. Th e tumors were measured tri-weekly and weighed at autopsy 21 days post therapy. Activity accumulation steadily increased in the tumors reachi ng 21% of the injected dose per gram of tumor (ID/g) at 144 h. At that time, the %ID/g in the tumor was 3 times higher than that in blood an d the liver and 8 times higher than in other major organs. On day 10 p ost-therapy, 16 of the 19 control mice had tumor volumes between 1 and 3 cm3, while none of the treated tumors ever reached 1 cm3 in size. A t autopsy, a 12-fold tumor weight difference (p=0.0001) was observed b etween control and treated mice (2.4g vs. 0.2g average weight, respect ively). In summary, breast cancer CEA was specifically targeted with T 84.66 allowing good tumor localization as well as significant tumor gr owth inhibition. Given the significant expression of CEA in breast can cer, this tumor should be included into the CEA-expressing malignancie s for targeting with anti-CEA MAbs.