PMID- 12560234
OWN - NLM
STAT- MEDLINE
DCOM- 20030819
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 1
DP  - 2003 Jul 1
TI  - Intranodal injection of semimature monocyte-derived dendritic cells induces T 
      helper type 1 responses to protein neoantigen.
PG  - 36-42
AB  - Dendritic cells (DCs) represent the most potent antigen-presenting cells of the 
      immune system capable of initiating primary immune responses to neoantigens. Here 
      we characterize the primary CD4 T-cell immune response to protein keyhole limpet 
      hemocyanin (KLH) in 5 metastatic melanoma patients undergoing a tumor 
      peptide-based dendritic cell vaccination trial. Monocyte-derived dendritic cells 
      displaying a semimature phenotype, as defined by surface markers, were loaded ex 
      vivo with antigen and injected intranodally at weekly intervals for 4 weeks. All 
      patients developed a strong and long-lasting delayed-type hypersensitivity 
      reactivity to KLH, which correlated with the induction of KLH-dependent 
      proliferation of CD4 T cells in vitro. Secondary in vitro stimulation with KLH 
      showed significant increase in interferon-gamma and interleukin-2 (IL-2) but not 
      IL-4, IL-5, nor IL-10 secretion by bulk T cells. On the single-cell level, most 
      TH1 cells among in vitro-generated KLH-specific T-cell lines confirmed the 
      preferential induction of a KLH-specific type 1 T helper immune response. 
      Furthermore, the induction of KLH-specific antibodies of the IgG2 subtype may 
      reflect the induction of a type 1 cytokine profile in vivo after vaccination. Our 
      results indicate that intranodal vaccination with semimature DCs can prime 
      strong, long-lasting CD4 T-cell responses with a TH1-type cytokine profile in 
      cancer patients.
FAU - Gilliet, Michel
AU  - Gilliet M
AD  - Department of Dermatology, University of Zurich, Gloriastrasse 31, 8091 Zurich, 
      Switzerland.
FAU - Kleinhans, Martin
AU  - Kleinhans M
FAU - Lantelme, Erica
AU  - Lantelme E
FAU - Schadendorf, Dirk
AU  - Schadendorf D
FAU - Burg, Gunter
AU  - Burg G
FAU - Nestle, Frank O
AU  - Nestle FO
LA  - eng
PT  - Journal Article
DEP - 20030130
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cytokines)
RN  - 9013-72-3 (Hemocyanins)
RN  - FV4Y0JO2CX (keyhole-limpet hemocyanin)
SB  - IM
MH  - Antibody Formation
MH  - Antigens, Neoplasm/immunology
MH  - Cell Culture Techniques/methods
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/cytology/*immunology/*transplantation
MH  - Hemocyanins/immunology
MH  - Humans
MH  - Hypersensitivity, Delayed
MH  - Immunity, Cellular
MH  - Immunotherapy, Adoptive/*methods
MH  - Injections, Intralymphatic
MH  - Lymphocyte Activation
MH  - Melanoma/pathology/*therapy
MH  - Monocytes/cytology
MH  - T-Lymphocytes/immunology
MH  - Th1 Cells/*immunology
EDAT- 2003/02/01 04:00
MHDA- 2003/08/20 05:00
CRDT- 2003/02/01 04:00
PHST- 2003/02/01 04:00 [pubmed]
PHST- 2003/08/20 05:00 [medline]
PHST- 2003/02/01 04:00 [entrez]
AID - S0006-4971(20)53973-6 [pii]
AID - 10.1182/blood-2002-07-2274 [doi]
PST - ppublish
SO  - Blood. 2003 Jul 1;102(1):36-42. doi: 10.1182/blood-2002-07-2274. Epub 2003 Jan 
      30.