Carcinoembryonic Antigen (CEA)-Based Cancer Vaccines: Recent Patents and Antitumor Effects from Experimental Models to Clinical Trials

Mario      Turriziani; Massimo      Fantini; Monica      Benvenuto; Valerio      Izzi; Laura      Masuelli; Pamela      Sacchetti; Andrea      Modesti; Roberto      Bei

Abstract

Carcinoembryonic antigen (CEA), a glycosylated protein of MW 180 kDa, is overexpressed in a wide range of human carcinomas, including colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Accordingly, CEA is one of several oncofetal antigens that may serve as a target for active anti-cancer specific immunotherapy. Experimental results obtained by employing animal models have supported the design of clinical trials using a CEA-based vaccine for the treatment of different types of human cancers. This review reports findings from experimental models and clinical evidence on the use of a CEA-based vaccine for the treatment of cancer patients. Among the diverse CEA-based cancer vaccines, DCs- and recombinant viruses-based vaccines seem the most valid. However, although vaccination was shown to induce a strong immune response to CEA, resulting in a delay in tumor progression and prolonged survival in some cancer patients, it failed to eradicate the tumor in most cases, owing partly to the negative effect exerted by the tumor microenvironment on immune response. Thus, in order to develop more efficient and effective cancer vaccines, it is necessary to design new clinical trials combining cancer vaccines with chemotherapy, radiotherapy and drugs which target those factors responsible for immunosuppression of immune cells. This review also discusses relevant patents relating to the use of CEA as a cancer vaccine.

Keywords: Cancer, CEA, CTL, immunotherapy, tumor antigen, vaccine, chemotherapy, radiotherapy, recombinant viruses-based vaccines, glycosylated protein