Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice.

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.

• Authors: Karsten Mahnke, Yingjie Qian, Sabine Fondel, Juergen Brueck, Christian Becker, Alexander H Enk
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 15 Pg. 7007-12 (Aug 01 2005) ISSN: 0008-5472 [Print] United States
• PMID: 16061687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neoplasm
• Antigens, CD
• Cancer Vaccines
• DEC-205 receptor
• Epitopes, T-Lymphocyte
• Immunoconjugates
• Lectins, C-Type
• Membrane Glycoproteins
• Minor Histocompatibility Antigens
• Neoplasm Proteins
• Pmel protein, mouse
• Receptors, Cell Surface
• gp100 Melanoma Antigen
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Animals
• Antibodies, Neoplasm (biosynthesis, immunology)
• Antigens, CD (immunology, therapeutic use)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology, therapeutic use)
• CpG Islands (immunology)
• Dendritic Cells (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Female
• Immunoconjugates (immunology, therapeutic use)
• Immunotherapy, Active (methods)
• Intramolecular Oxidoreductases (immunology, therapeutic use)
• Lectins, C-Type (immunology, therapeutic use)
• Lymphocyte Activation
• Melanoma, Experimental (immunology, prevention & control, therapy)
• Membrane Glycoproteins (immunology, therapeutic use)
• Mice
• Minor Histocompatibility Antigens
• Neoplasm Proteins (immunology, therapeutic use)
• Receptors, Cell Surface (immunology, therapeutic use)
• gp100 Melanoma Antigen