Back to Search Start Over

Rapid Induction of Tumor-specific Type 1 T Helper Cells in Metastatic Melanoma Patients by Vaccination with Mature, Cryopreserved, Peptide-loaded Monocyte-derived Dendritic Cells

Authors :
Nikolaus Romani
Erwin S. Schultz
Susanne Ebner
Petra Woerl
Bernadette Feuerstein
Peter O. Fritsch
Gerold Schuler
Beatrice Schuler-Thurner
Georg Weinlich
Thomas G. Berger
Armin Bender
Source :
The Journal of Experimental Medicine
Publication Year :
2002
Publisher :
Rockefeller University Press, 2002.

Abstract

There is consensus that an optimized cancer vaccine will have to induce not only CD8+ cytotoxic but also CD4+ T helper (Th) cells, particularly interferon (IFN)-γ–producing, type 1 Th cells. The induction of strong, ex vivo detectable type 1 Th cell responses has not been reported to date. We demonstrate now that the subcutaneous injection of cryopreserved, mature, antigen-loaded, monocyte-derived dendritic cells (DCs) rapidly induces unequivocal Th1 responses (ex vivo detectable IFN-γ–producing effectors as well as proliferating precursors) both to the control antigen KLH and to major histocompatibility complex (MHC) class II–restricted tumor peptides (melanoma-antigen [Mage]-3.DP4 and Mage-3.DR13) in the majority of 16 evaluable patients with metastatic melanoma. These Th1 cells recognized not only peptides, but also DCs loaded with Mage-3 protein, and in case of Mage-3DP4–specific Th1 cells IFN-γ was released even after direct recognition of viable, Mage-3–expressing HLA-DP4+ melanoma cells. The capacity of DCs to rapidly induce Th1 cells should be valuable to evaluate whether Th1 cells are instrumental in targeting human cancer and chronic infections.

Details

ISSN :
15409538 and 00221007
Volume :
195
Database :
OpenAIRE
Journal :
Journal of Experimental Medicine
Accession number :
edsair.doi.dedup.....e03d4fc9cd0001126361528bbd0092a3