Optimization of the sequence of antigen loading and CD40-ligand-induced maturation of dendritic cells.
Dendritic cells (DCs), matured by CD40-ligand (CD40L), undergo marked changes in their ability to process and present antigen, resulting in augmented lymphocyte stimulatory activity. We demonstrate that the form of the tumor antigen (peptide or genetic material) used to load the DCs dictates the required sequence of antigen loading and maturation for antitumor immunotherapy. Optimal stimulation of carcinoembryonic antigen (CEA)-specific CTLs by peptide-loaded DCs occurs when DCs from cancer patients are matured with CD40L before exposure to CEA peptide, whereas optimal stimulation by RNA-transfected DCs occurs when the DCs are loaded with CEA RNA before maturation with CD40L.
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
M A
MA
Morse
H K
HK
Lyerly
E
E
Gilboa
E
E
Thomas
S K
SK
Nair
D019013:CD40 Antigens / Q000276:immunology* / Q000502:physiology; D023201:CD40 Ligand; D002272:Carcinoembryonic Antigen / Q000276:immunology* / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D019013:CD40 Antigens; D002272:Carcinoembryonic Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D023201:CD40 Ligand