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Science. 2015 May 15;348(6236):803-8. doi: 10.1126/science.aaa3828. Epub 2015 Apr 2.

Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells.

Author information

  • 1Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA. bcarreno@dom.wustl.edu.
  • 2Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
  • 3Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
  • 4Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
  • 5EMD Millipore Corporation, Billerica, MA, USA.

Abstract

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-β 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00683670.

Copyright © 2015, American Association for the Advancement of Science.

PMID:
25837513
[PubMed - indexed for MEDLINE]
PMCID:
PMC4549796
Free PMC Article
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