CD40 triggering increases the efficiency of dendritic cells for antitumoral immunization.
Recent studies have shown the importance of triggering CD40 molecules to enhance the efficiency of dendritic cells (DCs) as antigen-presenting cells (APCs). The P198 and P1A tumor antigens, which are expressed by mastocytoma P815, have been assessed for their immunogenicity using different modes of immunization. We measured CTL responses induced in vivo with antigenic peptides P198 and P1A loaded onto bone marrow-derived DCs that had matured as a consequence of CD40-CD40L interactions. CD40L-transfected 3T3 fibroblasts were used as a source of CD40L signal. Our results show that this mode of DC activation considerably improves their ability to induce CTLs against P198 and P1A antigens in vivo as compared to untreated DCs. We also show that immunizations carried out with CD40L-activated DCs loaded with the P1A peptide induce a very efficient protection against a lethal challenge with P815 tumor cells, which express P1A. Our results indicate that the efficiency of DC-based vaccines used in clinical trials of cancer immunotherapy could be increased significantly by triggering DCs via CD40 prior to immunization.
Laboratory of Experimental Surgery, Université de Liège, Liège, Belgium.
Naïma
N
Mazouz
Annie
A
Ooms
Véronique
V
Moulin
Sonja
S
Van Meirvenne
Catherine
C
Uyttenhove
Gérard
G
Degiovanni
D016475:3T3 Cells; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods*
D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D023201:CD40 Ligand