Carcinoembryonic Antigen

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.

Carcinoembryonic antigen (CEA), as one of the common tumor markers, is a human glycoprotein involved in cell adhesion and is expressed during human fetal development. Since the birth of human, CEA expression is largely inhibited, with only low levels in the plasma of healthy adults. Generally, CEA will overexpressed in many cancers, including gastric, breast, ovarian, lung, and pancreatic cancers, especially colorectal cancer. As one of the important tumor markers, the detection of CEA has great significance in differential diagnosis, condition monitoring and therapeutic evaluation of diseases. Conventional CEA testing typically uses immunoassay methods. However, immunoassay methods require complex and expensive instruments and professional personnel to operate. Moreover, radioactive element may cause certain damage to the human body, which limits their wide application. In the past few years, biosensors, especially aptamer-based biosensors, have attracted extensive attention due to their high sensitivity, good selectivity, high accuracy, fast response and low cost. This review briefly classifies and describes the advance in optical and electrochemical aptamer biosensors for CEA detection, also explains and compares their advantages and disadvantages.

In this work, a sandwich-type electrochemical immunosensor for carcinoembryonic antigen (CEA) detection has been constructed and tested. Unlike many other sensors using external electrochemical species in the electrolyte to generate an electrochemical signal, a ferrocene derivative has been integrated into the design of the sensor to provide an internal reporting system, allowing detection of CEA in buffers and biological samples. Gold nanoparticles, which have been used to increase the conductivity of sensing surfaces, also carry immobilized secondary anti-CEA and a ferrocene derivative. The shelf life testing of the sensor shows good performance after storage for 4 weeks. The sensor has been calibrated against different concentration of the target protein using square wave voltammetry. The calibration curve has been obtained in the range of 0.05-20ngmL-1, and the detection limit for CEA is ~ 0.01ngmL-1. The capability of the immunosensor has been verified by performing detection of CEA in human serum samples.