Enhanced molecular mimicry of CEA using photoaffinity crosslinked C3d peptide.
Antigen mimicry of using anti-idiotypic antibodies for use as cancer vaccines has been disappointing due to the weak immunogenicity of immunoglobulin variable domains. To enhance the immunogenicity of an anti-idiotype vaccine we incorporated a molecular adjuvant peptide into the antibody. The peptide is derived from the C3d region known to bind CR2 receptors on B-cells. A photoreactive peptide is synthesized that affinity-labels a single site in the antibody variable domain. The molecular adjuvant peptide is crosslinked to the anti-idiotype mimetic by chemical means without modifying other sites on the antibody. The C3d-conjugated anti-idiotype antibody induces a strong idiotype and antigen-specific response in mice.
Lou
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Immpheron, Inc., Lexington, KY 40509, USA.
Kohler
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D000241:Adenosine / Q000031:analogs & derivatives / Q000737:chemistry; D000345:Affinity Labels / Q000737:chemistry; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001386:Azides / Q000737:chemistry; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015933:Complement C3d / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D017464:Receptors, Complement 3d / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000345:Affinity Labels; D000888:Antibodies, Anti-Idiotypic; D001386:Azides; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D010455:Peptides; D017464:Receptors, Complement 3d; C012760:8-azidoadenosine; D015933:Complement C3d; D000241:Adenosine