PMID- 22371843
OWN - NLM
STAT- MEDLINE
DCOM- 20130220
LR  - 20211021
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 20
IP  - 5
DP  - 2012 May
TI  - Dendritic cells loaded with mRNA encoding full-length tumor antigens prime CD4+ 
      and CD8+ T cells in melanoma patients.
PG  - 1063-74
LID - 10.1038/mt.2012.11 [doi]
AB  - It is generally thought that dendritic cells (DCs) loaded with full-length tumor 
      antigen could improve immunotherapy by stimulating broad T-cell responses and by 
      allowing treatment irrespective of the patient's human leukocyte antigen (HLA) 
      type. To investigate this, we determined the specificity of T cells from melanoma 
      patients treated with DCs loaded with mRNA encoding a full-length tumor antigen 
      fused to a signal peptide and an HLA class II sorting signal, allowing 
      presentation in HLA class I and II. In delayed-type hypersensitive (DTH)-biopsies 
      and blood, we found functional CD8(+) and CD4(+) T cells recognizing novel 
      treatment-antigen-derived epitopes, presented by several HLA types. Additionally, 
      we identified a CD8(+) response specific for the signal peptide incorporated to 
      elicit presentation by HLA class II and a CD4(+) response specific for the fusion 
      region of the signal peptide and one of the antigens. This demonstrates that the 
      fusion proteins contain newly created immunogenic sequences and provides evidence 
      that ex vivo-generated mRNA-modified DCs can induce effector CD8(+) and CD4(+) T 
      cells from the naive T-cell repertoire of melanoma patients. Thus, this work 
      provides definitive proof that DCs presenting the full antigenic spectrum of 
      tumor antigens can induce T cells specific for novel epitopes and can be 
      administered to patients irrespective of their HLA type.
FAU - Van Nuffel, An M T
AU  - Van Nuffel AM
AD  - Laboratory of Molecular and Cellular Therapy, Department of 
      Immunology-Physiology, Medical School of the Vrije Universiteit Brussel (VUB), 
      Brussels, Belgium.
FAU - Benteyn, Daphne
AU  - Benteyn D
FAU - Wilgenhof, Sofie
AU  - Wilgenhof S
FAU - Pierret, Lauranne
AU  - Pierret L
FAU - Corthals, Jurgen
AU  - Corthals J
FAU - Heirman, Carlo
AU  - Heirman C
FAU - van der Bruggen, Pierre
AU  - van der Bruggen P
FAU - Coulie, Pierre G
AU  - Coulie PG
FAU - Neyns, Bart
AU  - Neyns B
FAU - Thielemans, Kris
AU  - Thielemans K
FAU - Bonehill, Aude
AU  - Bonehill A
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120228
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (HLA-D Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigen Presentation
MH  - Antigens, Neoplasm/genetics/*immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/immunology/*transplantation
MH  - Electroporation
MH  - HLA-D Antigens/genetics/*immunology
MH  - Histocompatibility Antigens Class I/genetics/*immunology
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Lymphocyte Activation
MH  - Melanoma/immunology/pathology/*therapy
MH  - Molecular Sequence Data
MH  - Protein Sorting Signals
MH  - RNA, Messenger/genetics/*immunology
MH  - Skin Neoplasms/immunology/pathology/*therapy
MH  - Transfection
PMC - PMC3345975
EDAT- 2012/03/01 06:00
MHDA- 2013/02/21 06:00
PMCR- 2013/05/01
CRDT- 2012/02/29 06:00
PHST- 2012/02/29 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2013/02/21 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - S1525-0016(16)31946-3 [pii]
AID - 10.1038/mt.2012.11 [doi]
PST - ppublish
SO  - Mol Ther. 2012 May;20(5):1063-74. doi: 10.1038/mt.2012.11. Epub 2012 Feb 28.