CARBOHYDRATE ANTIGENS AS TARGETS FOR ACTIVE SPECIFIC IMMUNOTHERAPY

Carbohydrate antigens such as GM2, GD2 and GD3 (gangliosides), Lewis(y ) and globo-H (neutral glycolipids and glycoproteins), and Tn, TF and sTn (glycoproteins) are overexpressed in a variety of cancers. Antibod ies against several of these carbohydrate antigens have been detected in sera from patients treated with cancer vaccines, and have been asso ciated with a more favorable prognosis. Clinical responses have been r eported after treatment with monoclonal antibodies against some of the se antigens. Hence cell-surface carbohydrate antigens have been identi fied as suitable targets for immune attack by both active and passive immunotherapies. Different approaches have been adopted to induce immu ne responses against these carbohydrate antigens. These includes vacci nation with whole or lysed tumor cells, purified or synthetic carbohyd rates, immunogenic carbohydrate derivatives, or carbohydrates conjugat ed with immunogenic carriers and administered with immunological adjuv ants. In the case of gangliosides, immunization with either whole tumo r cells or cell lysates has only occasionally induced responses agains t carbohydrate antigens, and the antibodies were generally IgM antibod ies of low titer. Compared with other methods of vaccination, conjugat e vaccines have consistently induced the highest titer of IgM and IgG antibodies against gangliosides and other carbohydrate antigens. Precl inical and clinical studies with conjugate carbohydrate vaccines have induced IgM and IgG antibody responses capable of inducing complement- mediated cytotoxicity of tumor cells in vitro and associated with prol onged disease-free and overall survival in patients.