A new mouse model for evaluating the immunotherapy of human colorectal cancer

A new murine model of human colorectal cancer was generated by crossing hum an carcinoembryonic antigen (CEA) transgenic mice (H-2K(b)) with adenomatou s polyposis coli (Apc1638N) knockout mice (H-2K(b)). The resulting hybrid m ice developed gastrointestinal polyps in 6-8 months that progressed to inva sive carcinomas with a similar pattern of dysplasia and CEA expression as o bserved in human colorectal cancer. These animals exhibited incomplete or p artial tolerance to CEA as evidenced by delayed growth of CEA-expressing tu mors and the inability to inhibit CEA-specific CTL responses. These results have important implications for understanding the role of CEA-specific imm unity in human colon cancer patients and suggest that vaccine strategies ta rgeting CEA may be feasible. This model provides a powerful system for eval uating antigen-specific tumor immunity against spontaneous tumors arising i n an orthotopic location and permits evaluation of therapeutic vaccine stra tegies for human colorectal cancer.