PMID- 25837513
OWN - NLM
STAT- MEDLINE
DCOM- 20150623
LR  - 20220409
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 348
IP  - 6236
DP  - 2015 May 15
TI  - Cancer immunotherapy. A dendritic cell vaccine increases the breadth and 
      diversity of melanoma neoantigen-specific T cells.
PG  - 803-8
LID - 10.1126/science.aaa3828 [doi]
AB  - T cell immunity directed against tumor-encoded amino acid substitutions occurs in 
      some melanoma patients. This implicates missense mutations as a source of 
      patient-specific neoantigens. However, a systematic evaluation of these putative 
      neoantigens as targets of antitumor immunity is lacking. Moreover, it remains 
      unknown whether vaccination can augment such responses. We found that a dendritic 
      cell vaccine led to an increase in naturally occurring neoantigen-specific 
      immunity and revealed previously undetected human leukocyte antigen (HLA) class 
      I-restricted neoantigens in patients with advanced melanoma. The presentation of 
      neoantigens by HLA-A*02:01 in human melanoma was confirmed by mass spectrometry. 
      Vaccination promoted a diverse neoantigen-specific T cell receptor (TCR) 
      repertoire in terms of both TCR-beta usage and clonal composition. Our results 
      demonstrate that vaccination directed at tumor-encoded amino acid substitutions 
      broadens the antigenic breadth and clonal diversity of antitumor immunity.
CI  - Copyright (c) 2015, American Association for the Advancement of Science.
FAU - Carreno, Beatriz M
AU  - Carreno BM
AD  - Department of Medicine, Division of Oncology, Washington University School of 
      Medicine, St. Louis, MO, USA. bcarreno@dom.wustl.edu.
FAU - Magrini, Vincent
AU  - Magrini V
AD  - Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
FAU - Becker-Hapak, Michelle
AU  - Becker-Hapak M
AD  - Department of Medicine, Division of Oncology, Washington University School of 
      Medicine, St. Louis, MO, USA.
FAU - Kaabinejadian, Saghar
AU  - Kaabinejadian S
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Science 
      Center, Oklahoma City, OK, USA.
FAU - Hundal, Jasreet
AU  - Hundal J
AD  - Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
FAU - Petti, Allegra A
AU  - Petti AA
AD  - Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
FAU - Ly, Amy
AU  - Ly A
AD  - Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
FAU - Lie, Wen-Rong
AU  - Lie WR
AD  - EMD Millipore Corporation, Billerica, MA, USA.
FAU - Hildebrand, William H
AU  - Hildebrand WH
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Science 
      Center, Oklahoma City, OK, USA.
FAU - Mardis, Elaine R
AU  - Mardis ER
AD  - Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
FAU - Linette, Gerald P
AU  - Linette GP
AD  - Department of Medicine, Division of Oncology, Washington University School of 
      Medicine, St. Louis, MO, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00683670
GR  - 5U54HG00307/HG/NHGRI NIH HHS/United States
GR  - P30 CA91842/CA/NCI NIH HHS/United States
GR  - P30 CA091842/CA/NCI NIH HHS/United States
GR  - U54 HG003079/HG/NHGRI NIH HHS/United States
GR  - R21 CA179695/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150402
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
SB  - IM
CIN - Science. 2015 May 15;348(6236):760-1. PMID: 25977539
CIN - Nat Rev Genet. 2015 May;16(5):259. PMID: 26065036
MH  - Amino Acid Substitution/immunology
MH  - Antigen Presentation
MH  - Antigens, Neoplasm/genetics/*immunology
MH  - Cancer Vaccines/immunology/*therapeutic use
MH  - Dendritic Cells/immunology/*transplantation
MH  - HLA-A2 Antigen/genetics/*immunology
MH  - Humans
MH  - Immunotherapy, Active/*methods
MH  - Melanoma/genetics/immunology/*therapy
MH  - Monitoring, Immunologic
MH  - Mutation
MH  - Receptors, Antigen, T-Cell, alpha-beta/immunology
MH  - Skin Neoplasms/genetics/immunology/*therapy
MH  - T-Lymphocytes/*immunology
PMC - PMC4549796
MID - NIHMS713231
EDAT- 2015/04/04 06:00
MHDA- 2015/06/24 06:00
PMCR- 2016/05/15
CRDT- 2015/04/04 06:00
PHST- 2014/11/27 00:00 [received]
PHST- 2015/03/19 00:00 [accepted]
PHST- 2015/04/04 06:00 [entrez]
PHST- 2015/04/04 06:00 [pubmed]
PHST- 2015/06/24 06:00 [medline]
PHST- 2016/05/15 00:00 [pmc-release]
AID - science.aaa3828 [pii]
AID - 10.1126/science.aaa3828 [doi]
PST - ppublish
SO  - Science. 2015 May 15;348(6236):803-8. doi: 10.1126/science.aaa3828. Epub 2015 Apr 
      2.