Carcinoembryonic antigen as a target to induce anti-tumor immune responses

Abstract

Identification of relevant targets for cancer therapy is a major goal in cancer research. In this field, the identification of tumor antigens has opened the possibility of inducing specific anti-tumor immune responses. Among these antigens, carcinoembryonic antigen (CEA) is especially relevant because CEA is expressed in a wide variety of adenocarcinomas such as colon, rectum, pancreas, gastric, breast, etc. The present review focuses on different strategies to induce anti-CEA immune responses. In a first group of strategies, the antigen is administered using viral and bacterial vectors expressing CEA, dendritic cells loaded with CEA protein, or dendritic cells transfected with DNA or RNA expressing CEA. A second group of strategies is based on immunizations with antigenic peptide determinants from CEA, rather than with immunogens containing the whole protein. This has been possible due to the identification of different peptide determinants from CEA, which when presented by MHC class I molecules, are recognized by T cytotoxic lymphocytes. More recently, due to the importance of CD4(+) T cells in the induction of immune responses, T helper peptides presented by MHC class II molecules have also been identified. To overcome the poor immunogenicity of CEA-derived peptide determinants, a common feature of self-antigens, their sequence has been modified to improve binding to MHC molecules or recognition by T cell receptors. Finally, in order to enhance immunization efficacy, some of these strategies have combined the administration of immunogens and cytokines or co-stimulatory molecules. Some of the immunization protocols developed are being tested in clinical trials with promising results. Thus, CEA may prove to be a valuable target antigen for the therapy of a high number of malignancies.