Mice Expressing the Human Carcinoembryonic Antigen

Abstract

A series of important studies have led to a relaxation in the paradigms overseeing self/nonself immunity. Antigens which are oncofetal and/or serve as markers of cellular differentiation that are overexpressed or ectopically expressed by malignant cells were believed not to be targets for immunotherapy because of host immune tolerance. That conclusion has been challenged in recent years by a series of studies indicating that antigenic determinants of self have not induced absolute immune tolerance. Thus, under specific immunological conditions, specific peptides from those antigens can be processed by the antigen-presenting machinery, bound in MHC groove and serve as targets for immune intervention (1–4). Those actions, in turn, offer the possibility that differentiation antigens, oncogenes and tumor-suppressor genes that are found in tumor cells may be considered targets for attack by the immune system (5–8). One of the tissue-specific, tumor-associated antigens that shows much higher expression levels on tumors than on corresponding normal epithelial is carcinoembryonic antigen (CEA). This chapter reviews recent data that offers convincing evidence that CEA can indeed be a target for vaccine-mediated therapy of human cancers. The first part briefly introduces the CEA gene family and the use of CEA as an indicator for tumor diagnosis and patient management. More in-depth examinations of those subjects have been published elsewhere (9,10). The second part introduces an experimental transgenic mouse model that expresses CEA as a self, tumor antigen. The major focus of the chapter is the development of an experimental model that can provide some important insights into CEA-based vaccine strategies. The final section summarizes some of the early clinical results in which CEA is the immunotherapeutic target.