Carbohydrate antigens as targets for active specific immunotherapy |
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Authors: | Govindaswami Ragupathi |
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Institution: | (1) Clinical Immunology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY-10021, USA, US |
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Abstract: | Carbohydrate antigens such as GM2, GD2 and GD3 (gangliosides), Lewisy and globo-H (neutral glycolipids and glycoproteins), and Tn, TF and sTn (glycoproteins) are overexpressed in a variety of
cancers. Antibodies against several of these carbohydrate antigens have been detected in sera from patients treated with cancer
vaccines, and have been associated with a more favorable prognosis. Clinical responses have been reported after treatment
with monoclonal antibodies against some of these antigens. Hence cell-surface carbohydrate antigens have been identified as
suitable targets for immune attack by both active and passive immunotherapies. Different approaches have been adopted to induce
immune responses against these carbohydrate antigens. These includes vaccination with whole or lysed tumor cells, purified
or synthetic carbohydrates, immunogenic carbohydrate derivatives, or carbohydrates conjugated with immunogenic carriers and
administered with immunological adjuvants. In the case of gangliosides, immunization with either whole tumor cells or cell
lysates has only occasionally induced responses against carbohydrate antigens, and the antibodies were generally IgM antibodies
of low titer. Compared with other methods of vaccination, conjugate vaccines have consistently induced the highest titer of
IgM and IgG antibodies against gangliosides and other carbohydrate antigens. Preclinical 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 prolonged disease-free and overall survival in patients.
Received: 6 August 1996 / Accepted: 20 September 1996 |
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Keywords: | Antigen Cancer Carbohydrate Gangliosides Immunotherapy Vaccine |
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