Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity.
Cytotoxic T lymphocytes (CTLs) are a critical component of the immune response to tumors. Tumor-derived peptide antigens targeted by CTLs are being defined for several human tumors and are potential immunogens for the induction of specific antitumor immunity. Dendritic cells (DC) are potent antigen-presenting cells (APCs) capable of priming CTL responses in vivo. Here we show that major histocompatibility complex class I-presented peptide antigen pulsed onto dendritic APCs induces protective immunity to lethal challenge by a tumor transfected with the antigen gene. The immunity is antigen specific, requiring expression of the antigen gene by the tumor target, and is eliminated by in vivo depletion of CD8+ T cells. Furthermore, mice that have rejected the transfected tumor are protected from subsequent challenge with the untransfected parent tumor. These results suggest that immunization strategies using antigen-pulsed DC may be useful for inducing tumor-specific immune responses.
Celluzzi
C M
CM
Department of Dermatology, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Mayordomo
J I
JI
Storkus
W J
WJ
Lotze
M T
MT
Falo
L D
LD
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007114:Immunization; D008546:Melanoma, Experimental / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000628:therapy*; D010446:Peptide Fragments / Q000627:therapeutic use*; D016019:Survival Analysis; D013945:Thymoma / Q000628:therapy
D010446:Peptide Fragments