Expression of transgenic carcinoembryonic antigen (CEA) in tumor‐prone mice: An animal model for CEA‐directed tumor immunotherapy

• Published in: International journal of cancer Vol. 72; no. 1; pp. 197 - 202
• Main Authors: Thompson, John A., Eades‐Perner, Anne‐Marie, Ditter, Margarethe, Muller, William J., Zimmermann, Wolfgang
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 03-07-1997; Wiley-Liss
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Carcinoembryonic Antigen - genetics; Carcinoembryonic Antigen - metabolism; Crosses, Genetic; Disease Models, Animal; Experimental tumors, general aspects; Female; Genes, erbB-2; Intestinal Neoplasms - genetics; Intestinal Neoplasms - metabolism; Lung Neoplasms - genetics; Male; Mammary Neoplasms, Experimental - genetics; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Simian virus 40 - genetics; Tumors; Human origin; Animal model; Carcinoma; Tumor associated antigen; Rodentia; Transgenic animal; Hybrid; Malignant tumor; Carcinoembryonic antigen; Vertebrata; Mammalia; Mouse; Immunotherapy; Animal
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19970703)72:1<197::AID-IJC28>3.0.CO;2-F

Carcinoembryonic antigen (CEA) is a tumor marker for the most common forms of adenocarcinomas. We have previously described C57BL/6 mice transgenic for the complete human CEA gene. Compared with humans, these mice reveal a conserved spatiotemporal CEA expression pattern. To establish animal models for CEA‐targeted tumor immunotherapy, we have crossed CEA transgenic mice with mice that are genetically predisposed to tumor development. These immunocompetent animals should allow optimization of immunotherapy strategies for maximal destruction of tumor tissues with minimal damage to CEA‐expressing normal tissues. To develop a breast tumor model, CEA transgenic mice were cross‐bred with mice transgenic for the rat neu protooncogene controlled by the mouse mammary tumor virus long terminal repeat. Female offspring developed poorly differentiated breast tumors, none of which, however, expressed CEA. As a model for colorectal tumors, mice bearing a mutation in the Apc gene (Min mice) and the CEA transgene developed multiple intestinal adenomas with strong CEA expression in all tumor cells. CEA expression had no significant effect on tumor growth. Occasional, well‐differentiated breast adenocarcinomas in female offspring expressed CEA focally in tumor cells lining pseudolumina. Cross‐breeding ApcMin/+ mice with neu transgenic mice did not reveal a synergistic effect on the kinetics of breast tumor formation. Finally, CEA transgenic mice crossbred with mice transgenic for the SV40 large T antigen regulated by the surfactant protein‐C promoter, developed multiple lung adenocarcinomas that revealed a mosaic CEA expression pattern. Int. J. Cancer 72:197–202, 1997. © 1997 Wiley‐Liss Inc.