title: Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells.
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.
authors.affiliation: Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA. bcarreno@dom.wustl.edu.
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Carreno
authors.affiliation: Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Magrini
authors.affiliation: Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Becker-Hapak
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: Saghar
authors.initials: S
authors.lastname: Kaabinejadian
authors.affiliation: Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jasreet
authors.initials: J
authors.lastname: Hundal
authors.affiliation: Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Allegra A
authors.initials: AA
authors.lastname: Petti
authors.affiliation: Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Ly
authors.affiliation: EMD Millipore Corporation, Billerica, MA, USA.
authors.forename: Wen-Rong
authors.initials: WR
authors.lastname: Lie
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Hildebrand
authors.affiliation: Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
authors.affiliation: Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Linette
mesh_terms: D019943:Amino Acid Substitution / Q000276:immunology; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D015166:Monitoring, Immunologic; D009154:Mutation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta
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