Mage-3 and influenza-matrix peptide-specific cytotoxic T cells are inducible in terminal stage HLA-A2.1+ melanoma patients by mature monocyte-derived dendritic cells.
Dendritic cell (DC) vaccination, albeit still in an early stage, is a promising strategy to induce immunity to cancer. We explored whether DC can expand Ag-specific CD8+ T cells even in far-advanced stage IV melanoma patients. We found that three to five biweekly vaccinations of mature, monocyte-derived DC (three vaccinations of 6 x 106 s.c. followed by two i.v. ones of 6 and 12 x 106, respectively) pulsed with Mage-3A2.1 tumor and influenza matrix A2. 1-positive control peptides as well as the recall Ag tetanus toxoid (in three of eight patients) generated in all eight patients Ag-specific effector CD8+ T cells that were detectable in blood directly ex vivo. This is the first time that active, melanoma peptide-specific, IFN-gamma-producing, effector CD8+ T cells have been reliably observed in patients vaccinated with melanoma Ags. Therefore, our DC vaccination strategy performs an adjuvant role and encourages further optimization of this new immunization approach.
Schuler-Thurner
B
B
Department of Dermatology, University of Erlangen-Nuremberg, Erlangen, Germany. schuler@derma.med.uni-erlangen.de
Dieckmann
D
D
Keikavoussi
P
P
Bender
A
A
Maczek
C
C
Jonuleit
H
H
Röder
C
C
Haendle
I
I
Leisgang
W
W
Dunbar
R
R
Cerundolo
V
V
von Den Driesch
P
P
Knop
J
J
Bröcker
E B
EB
Enk
A
A
Kämpgen
E
E
Schuler
G
G
D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D036341:Intercellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009000:Monocytes / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D036341:Intercellular Signaling Peptides and Proteins; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D010455:Peptides; D013745:Tetanus Toxoid; D014763:Viral Matrix Proteins; C075525:A2-binding peptide