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 for m of the tumor antigen (peptide or genetic material) used to load the DCs dictates the required sequence of antigen loading and maturation f or antitumor immunotherapy, Optimal stimulation of carcinoembryonic an tigen (CEA)-specific CTLs by peptide-loaded DCs occurs when DCs from c ancer 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.