Modulating cell surface immunoreactivity by metabolic induction of unnatural carbohydrate antigens.
BACKGROUND
Sialic acid is a component of many tumor-associated oligosaccharide antigens. The repertoire of sialic acids presented by cells can be expanded to include unnatural variants by intercepting the sialic acid biosynthetic pathway with unnatural precursors. We explored whether unnatural cell surface sialosides produced by metabolism can act as neo-antigens and modulate the immunogenicity of cells.


RESULTS
Immunization of rabbits with synthetic conjugates of an unnatural sialic acid bound to keyhole limpet hemocyanin produced significant titers of antibodies that were specific for the structurally altered sialic acid. The antibodies recognized cells that were fed the unnatural biosynthetic precursor, and were capable of directing complement-mediated lysis.


CONCLUSIONS
Structural alteration of sialic acids replaces a tolerized self-antigen with an antigenic determinant. Incorporation of unnatural sialosides into cell surface glycoconjugates through biosynthetic means can alter the immunoreactivity of cells, providing new possibilities for tumor immunotherapy.
Lemieux
G A
GA
Department of Chemistry, University of California, Berkeley 94720, USA.
Bertozzi
C R
CR
D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000494:pharmacology; D000918:Antibody Specificity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis / Q000276:immunology; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D006367:HeLa Cells; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007114:Immunization; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits
D000276:Adjuvants, Immunologic; D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; D008562:Membrane Glycoproteins; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D019158:N-Acetylneuraminic Acid