Abstract
Anti (alpha)-DEC-205 antibodies target to the DEC-205 receptor that mediates antigen presentation to T cells by dendritic cells. To exploit these properties for immunization purposes, we conjugated the melanoma antigen tyrosinase-related protein (TRP)-2 to alphaDEC-205 antibodies and immunized mice with these conjugates together with dendritic cell-activating oligonucleotides (CpG). Upon injection of the melanoma cell line B16, alphaDEC-TRP immunized mice were protected against tumor growth. Even more important for clinical applications, we were able to substantially slow the growth of implanted B16 cells by injection of alphaDEC-TRP2 conjugates into tumor bearing hosts. Approximately 70% of the animals were cured from existing tumors by treatment with alphaDEC conjugates carrying two different melanoma antigens (TRP-2 and gp100). This protection was due to induction of melanoma-specific CD4 and CD8 responses. Thus, these data show that targeting of dendritic cells in situ by the means of antibody-antigen conjugates may be a novel way to induce long-lasting antitumor immunity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Neoplasm / biosynthesis
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Antibodies, Neoplasm / immunology
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Antigens, CD / immunology*
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Antigens, CD / therapeutic use
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cancer Vaccines / immunology*
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Cancer Vaccines / therapeutic use
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CpG Islands / immunology
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Dendritic Cells / immunology*
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Epitopes, T-Lymphocyte / immunology
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Female
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Immunoconjugates / immunology*
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Immunoconjugates / therapeutic use
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Immunotherapy, Active / methods
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Intramolecular Oxidoreductases / immunology*
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Intramolecular Oxidoreductases / therapeutic use
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Lectins, C-Type / immunology*
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Lectins, C-Type / therapeutic use
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Lymphocyte Activation
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Melanoma, Experimental / immunology
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Melanoma, Experimental / prevention & control
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Melanoma, Experimental / therapy*
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / therapeutic use
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Mice
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Minor Histocompatibility Antigens
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Neoplasm Proteins / immunology
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Neoplasm Proteins / therapeutic use
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Receptors, Cell Surface / immunology*
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Receptors, Cell Surface / therapeutic use
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gp100 Melanoma Antigen
Substances
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Antibodies, Neoplasm
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Antigens, CD
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Cancer Vaccines
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DEC-205 receptor
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Epitopes, T-Lymphocyte
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Immunoconjugates
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Lectins, C-Type
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Membrane Glycoproteins
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Minor Histocompatibility Antigens
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Neoplasm Proteins
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Pmel protein, mouse
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Receptors, Cell Surface
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gp100 Melanoma Antigen
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Intramolecular Oxidoreductases
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dopachrome isomerase