Cancer vaccines and carbohydrate epitopes

Tumor-associated carbohydrate antigens (TACA) result from the aberrant glycosylation that is seen with transformation to a tumor cell. The carbohydrate antigens that have been found to be tumor-associated include the mucin related Tn, Sialyl Tn, and Thomsen–Friedenreich antigens, the blood group Lewis related LewisY, Sialyl LewisX and Sialyl LewisA, and LewisX (also known as stage-specific embryonic antigen-1, SSEA-1), the glycosphingolipids Globo H and stage-specific embryonic antigen-3 (SSEA-3), the sialic acid containing glycosphingolipids, the gangliosides GD2, GD3, GM2, fucosyl GM1, and Neu5GcGM3, and polysialic acid. Recent developments have furthered our understanding of the T-independent type II response that is seen in response to carbohydrate antigens. The selection of a vaccine target antigen is based on not only the presence of the antigen in a variety of tumor tissues but also on the role this antigen plays in tumor growth and metastasis. These roles for TACAs are being elucidated. Newly acquired knowledge in understanding the T-independent immune response and in understanding the key roles that carbohydrates play in metastasis are being applied in attempts to develop an effective vaccine response to TACAs. The role of each of the above mentioned carbohydrate antigens in cancer growth and metastasis and vaccine attempts using these antigens will be described.

► TACAs result from aberrant glycosylation in tumor cells.
► TACAs discussed include: Truncated O-glycan antigens, Lewis structures, Globo H, SSEA-3, Gangliosides, polysialic acid.
► Recent advances provide a better understanding of the T-independent type II response.
► Cancer vaccines should target antigens with a role in tumor growth or metastasis.
► Severity of potential autoimmunity should be considered prior to vaccine creation.
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