1. A new mouse model for evaluating the immunotherapy of human colorectal cancer.
- Author
-
Hörig H, Wainstein A, Long L, Kahn D, Soni S, Marcus A, Edelmann W, Kucherlapati R, and Kaufman HL
- Subjects
- Adenocarcinoma immunology, Adenocarcinoma metabolism, Adenocarcinoma therapy, Animals, Carcinoembryonic Antigen immunology, Colorectal Neoplasms immunology, Colorectal Neoplasms therapy, Crosses, Genetic, Female, H-2 Antigens immunology, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Pregnancy, Tumor Cells, Cultured, Adenocarcinoma genetics, Carcinoembryonic Antigen genetics, Colorectal Neoplasms genetics, Disease Models, Animal, Genes, APC, H-2 Antigens genetics
- Abstract
A new murine model of human colorectal cancer was generated by crossing human carcinoembryonic antigen (CEA) transgenic mice (H-2K(b)) with adenomatous polyposis coli (Apc1638N) knockout mice (H-2K(b)). The resulting hybrid mice developed gastrointestinal polyps in 6-8 months that progressed to invasive carcinomas with a similar pattern of dysplasia and CEA expression as observed in human colorectal cancer. These animals exhibited incomplete or partial tolerance to CEA as evidenced by delayed growth of CEA-expressing tumors and the inability to inhibit CEA-specific CTL responses. These results have important implications for understanding the role of CEA-specific immunity in human colon cancer patients and suggest that vaccine strategies targeting CEA may be feasible. This model provides a powerful system for evaluating antigen-specific tumor immunity against spontaneous tumors arising in an orthotopic location and permits evaluation of therapeutic vaccine strategies for human colorectal cancer.
- Published
- 2001