6533b831fe1ef96bd12985bd

RESEARCH PRODUCT

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.

Rod DunbarBeatrice Schuler-thurnerJürgen KnopIna HaendleClaudia RöderEckhart KämpgenArmin BenderHelmut JonuleitGerhard SchulerChristian MaczekVincenzo CerundoloEva-b. BröckerP. Von Den DrieschPetra KeikavoussiWaltraud LeisgangAlexander EnkDetlef Dieckmann

subject

CD4-Positive T-LymphocytesCytotoxicity Immunologicmedicine.medical_treatmentInjections SubcutaneousImmunologyImmunization SecondaryEpitopes T-LymphocyteCD8-Positive T-LymphocytesLymphocyte ActivationCancer VaccinesMonocytesViral Matrix ProteinsAntigens NeoplasmTetanus ToxoidImmunology and AllergyMedicineCytotoxic T cellHumansMelanomaCells Culturedbusiness.industryMelanomaToxoidCell DifferentiationDendritic cellDendritic Cellsmedicine.diseaseNeoplasm ProteinsImmunizationImmunologyInjections IntravenousIntercellular Signaling Peptides and ProteinsbusinessPeptidesAdjuvantCD8Ex vivoT-Lymphocytes Cytotoxic

description

Abstract 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 × 106 s.c. followed by two i.v. ones of 6 and 12 × 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-γ-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.

10.4049/jimmunol.165.6.3492https://ora.ox.ac.uk/objects/uuid:b3385d39-f639-4e34-b662-f2c05b5b9375