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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
- 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.
- Subjects :
- Adult
Cytotoxicity, Immunologic
Male
Immunology
Biology
Major histocompatibility complex
Cancer Vaccines
Article
Interferon-gamma
T helper cells
Interleukin 21
Antigen
Antigens, Neoplasm
Interferon
medicine
Humans
Immunology and Allergy
Cytotoxic T cell
dendritic cells
Neoplasm Metastasis
Antigen-presenting cell
Melanoma
neoplasms
Aged
CD40
Vaccination
Middle Aged
Th1 Cells
CD4+ T cells
Neoplasm Proteins
tumor immunity
Kinetics
biology.protein
Interleukin-2
Female
Interleukin-4
Immunologic Memory
CD8
medicine.drug
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 195
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....e03d4fc9cd0001126361528bbd0092a3