PMID- 16540682
OWN - NLM
STAT- MEDLINE
DCOM- 20060503
LR  - 20201212
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 6
DP  - 2006 Mar 15
TI  - Human leukocyte antigen-A2-restricted CTL responses to mutated BRAF peptides in 
      melanoma patients.
PG  - 3287-93
AB  - Mutated BRAF (BRAF(V600E)) is a potential immunotherapeutic target for melanoma 
      because of its tumor specificity and expression in the majority of these lesions 
      derived from different patients. BRAF(V600E) is expressed intracellularly and not 
      on the cell surface, therefore providing a target for T cells but not B cells. 
      Demonstration of patients' T cell responses to BRAF(V600E) would suggest the 
      feasibility of active specific immunotherapy targeting the mutation in these 
      patients. In the present study, BRAF(V600E) peptides with putative binding sites 
      for human leukocyte antigen (HLA)-A2 were used to stimulate T lymphocytes of 
      HLA-A2-positive melanoma patients. Four of five patients with 
      BRAF(V600E)-positive lesions showed lymphoproliferative responses to BRAF(V600E) 
      peptide stimulation. These responses were specific for the mutated epitope and 
      HLA-A2 was restricted in three patients. Lymphocytes from these three patients 
      were cytotoxic against HLA-A2-matched BRAF(V600E)-positive melanoma cells. None 
      of the four patients with BRAF(V600E)-negative lesions and none of five healthy 
      donors had lymphoproliferative responses specific for the mutated epitope. The 
      high prevalence (approximately 50%) of HLA-A2 among melanoma patients renders 
      HLA-A2-restricted BRAF(V600E) peptides attractive candidate vaccines for these 
      patients.
FAU - Somasundaram, Rajasekharan
AU  - Somasundaram R
AD  - The Wistar Institute, Philadelphia, PA 19104, USA.
FAU - Swoboda, Rolf
AU  - Swoboda R
FAU - Caputo, Laura
AU  - Caputo L
FAU - Otvos, Laszlo
AU  - Otvos L
FAU - Weber, Barbara
AU  - Weber B
FAU - Volpe, Patricia
AU  - Volpe P
FAU - van Belle, Patricia
AU  - van Belle P
FAU - Hotz, Susan
AU  - Hotz S
FAU - Elder, David E
AU  - Elder DE
FAU - Marincola, Francesco M
AU  - Marincola FM
FAU - Schuchter, Lynn
AU  - Schuchter L
FAU - Guerry, DuPont
AU  - Guerry D
FAU - Czerniecki, Brian J
AU  - Czerniecki BJ
FAU - Herlyn, Dorothee
AU  - Herlyn D
LA  - eng
GR  - CA10815/CA/NCI NIH HHS/United States
GR  - CA25874/CA/NCI NIH HHS/United States
GR  - CA93372/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Cytokines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptide Fragments)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - Binding Sites
MH  - Cell Line, Tumor
MH  - Cytokines/immunology/metabolism
MH  - Epitopes, T-Lymphocyte/genetics/immunology
MH  - HLA-A Antigens/*immunology
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Immunotherapy, Adoptive
MH  - Lymphocyte Activation
MH  - Melanoma/*immunology/*therapy
MH  - Mutation
MH  - Peptide Fragments/genetics/immunology/therapeutic use
MH  - Proto-Oncogene Proteins B-raf/genetics/*immunology/*therapeutic use
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2006/03/17 09:00
MHDA- 2006/05/04 09:00
CRDT- 2006/03/17 09:00
PHST- 2006/03/17 09:00 [pubmed]
PHST- 2006/05/04 09:00 [medline]
PHST- 2006/03/17 09:00 [entrez]
AID - 66/6/3287 [pii]
AID - 10.1158/0008-5472.CAN-05-1932 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Mar 15;66(6):3287-93. doi: 10.1158/0008-5472.CAN-05-1932.