Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice.
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.
Mahnke
Karsten
K
Department of Dermatology, University of Heidelberg, Heidelberg, Germany. karsten.mahnke@med.uni-heidelberg.de
Qian
Yingjie
Y
Fondel
Sabine
S
Brueck
Juergen
J
Becker
Christian
C
Enk
Alexander H
AH
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D018796:Immunoconjugates / Q000276:immunology* / Q000627:therapeutic use; D016233:Immunotherapy, Active / Q000379:methods; D019746:Intramolecular Oxidoreductases / Q000276:immunology* / Q000627:therapeutic use; D037181:Lectins, C-Type / Q000276:immunology* / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins / Q000276:immunology / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000627:therapeutic use; D058951:gp100 Melanoma Antigen
D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D019496:Cancer Vaccines; C093569:DEC-205 receptor; D018984:Epitopes, T-Lymphocyte; D018796:Immunoconjugates; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; C548642:Pmel protein, mouse; D011956:Receptors, Cell Surface; D058951:gp100 Melanoma Antigen; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase