Carcinoembryonic antigen-based vaccines

Carcinoembryonic antigen (CEA) is a glycoprotein that is normally expressed in certain parts of the body and commonly overexpressed in most carcinomas of the colon, rectum, breast, lung, pancreas, and gastrointestinal tract. Increased expression of CEA promotes increased intercellular adhesions, which may lead to metastasis. Carcinoembryonic antigen is often used as a serologic marker of malignancy because of its overexpression in cancer as well as its measurability in serum. However, because CEA is normally expressed in the body, the immune system commonly becomes tolerant to it. If this tolerance can be overcome without leading to autoimmune disease, CEA vaccination therapy could be immensely beneficial to cancer patients. A number of preclinical and clinical studies have been conducted on the use of recombinant CEA-vaccinia virus vaccines and recombinant ALVAC-CEA vaccines. In general, the vaccines have been well tolerated and effective at inducing CEA-specific cytotoxic T-cell responses, especially when used in the presence of the T-cell costimulatory molecule B7.1. "Prime and boost" techniques combining both types of vaccines and the addition of cytokines such as granulocyte-macrophage colony-stimulating factor have resulted in enhanced T-cell responses. The combination of vaccinia or ALVAC vaccines with a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3) has also stimulated significant T-cell increases. This review summarizes these studies and discusses the role of CEA in cancer immunotherapy.