A new mouse model for evaluating the immunotherapy of human colorectal cancer.
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.
Hörig
H
H
Department of Surgery, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Wainstein
A
A
Long
L
L
Kahn
D
D
Soni
S
S
Marcus
A
A
Edelmann
W
W
Kucherlapati
R
R
Kaufman
H L
HL
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000276:immunology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D017491:Genes, APC; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse