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Carcinoembryonic Antigen as a Target for Therapeutic Anticancer Vaccines: A Review

From Aventis Pasteur Ltd and Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada.

Address reprint requests to Neil L. Berinstein, MD, Toronto-Sunnybrook Regional Cancer Centre, 2075 Bayview Ave, Toronto, Ontario M4N 3M5, Canada; email: neil.berinstein{at}aventis.com

PURPOSE: To describe the features of carcinoembryonic antigen (CEA) that are important for its use in vaccination approaches and review the clinical experience with therapeutic vaccines targeting CEA.

METHODS: A PubMed search was performed on CEA, along with various qualifiers such as cancer vaccines, epitopes, and function. Relevant articles were reviewed.

RESULTS: CEA is a member of the immunoglobulin supergene family and may play a role in tumorigenesis. CEA protein is processed and presented on major histocompatibility complex (MHC) proteins for multiple alleles, including HLA A2, A3, and A24. T lymphocytes from healthy volunteers and cancer patients can recognize the processed epitopes of CEA and can become activated to lyse CEA-expressing tumors. Therapeutic vaccination approaches that have targeted CEA include vaccination with recombinant CEA protein, CEA anti-idiotype antibodies, and dendritic cells pulsed with agonist epitopes of CEA. Humoral responses have predominantly been induced with the first two approaches, whereas CD4 and CD8 responses, disease stabilization, and even objective clinical responses have been seen with the dendritic cell approach. Recently, CEA-poxvirus vectors encoding CEA and costimulatory molecules such as B7.1 have been shown to be safe and to induce increases in the frequency of T-cell precursors that recognize processed epitopes of CEA presented on MHC class 1 molecules. Disease stabilization has been seen in up to 37% of patients treated with these vaccines.

CONCLUSION: Tolerance to CEA in patients with cancer can be overcome with several different vaccination approaches, and such vaccinations are safe and immunologically active. Poxvirus-based vaccines can reproducibly generate T-cell responses to CEA and to tumors expressing CEA. Clinical activity has been seen with poxvirus or dendritic cell approaches. Other approaches are also being explored.

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