Antibody targeting studies in a transgenic murine model of spontaneous colorectal tumors

Monoclonal antibodies (mAbs) have been used to treat malignancies in humans with varying degrees of success. Progress has been hindered by the lack of suitable animal models, which would ideally consist of immunocompetent ani mals that are tolerant to tumor-associated antigens. Suitable models would allow the study and optimization of anti-tumor immunotherapy. We describe a murine model for the study of immunotherapy in colorectal cancers. Carcino embryonic antigen (CEA) is a cell-surface glycoprotein that is expressed on normal human intestinal epithelium and that is overexpressed in intestinal tumors. Mice that are transgenic for the human CEA gene (CEA.Tg) were cros sed with multiple intestinal neoplasia (MIN) mice. MIN mice carry a germlin e APC mutation and are prone to the development of intestinal adenomas. The offspring from the MIN x CEA.Tg cross developed intestinal adenomas that w ere shown by immunohistochemistry to overexpress CEA. Pharmacokinetic studi es by using I-125-labeled anti-CEA mAb PR1A3 showed rapid localization of a ntibody to tissues expressing CEA, especially the gastrointestinal tract. M acroscopic and microscopic radioautographic analysis of the gastrointestina l tracts from MIN/CEA.Tg mice indicated that PR1A3 targeted and was retaine d in tumors at levels higher than in areas of normal gut. These results dem onstrate the utility of the MIN/CEA.Tg mouse as a model for the study of an ti-CEA immunotherapy and, furthermore, demonstrate the efficiency of tumor localization by PR1A3.