title: MHC class I-presented tumor antigens identified in ovarian cancer by immunoproteomic analysis are targets for T-cell responses against breast and ovarian cancer.
abstract: OBJECTIVE
  The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-cell responses in humans.
  
  
  METHODS
  Mixtures of human leukocyte antigen A2 (HLA-A2)-binding ovarian cancer-associated peptides were used to activate naive T cells to generate antigen-specific T cells that could recognize ovarian and breast cancers in vitro. Combinations of these peptides (0.3 mg of each peptide or 1 mg of each peptide) were formulated into vaccines in conjunction with Montanide ISA-51 and granulocyte monocyte colony stimulating factor which were used to vaccinate patients with ovarian and breast cancer without evidence of clinical disease in parallel pilot clinical trials.
  
  
  RESULTS
  T cells specific for individual peptides could be generated in vitro by using mixtures of peptides, and these T cells recognized ovarian and breast cancers but not nonmalignant cells. Patient vaccinations were well tolerated with the exception of local erythema and induration at the injection site. Nine of the 14 vaccinated patients responded immunologically to their vaccine by inducing peptide-specific T-cell responses that were capable of recognizing HLA-matched breast and ovarian cancer cells.
  
  
  CONCLUSIONS
  Mixtures of specific peptides identified as naturally presented on cancer cells and capable of activating tumor-specific T cells in vitro also initiate or augment immune responses toward solid tumors in cancer patients.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27410, USA. michael.morse@duke.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: Angeles A
authors.initials: AA
authors.lastname: Secord
authors.forename: Kimberly
authors.initials: K
authors.lastname: Blackwell
authors.forename: Amy C
authors.initials: AC
authors.lastname: Hobeika
authors.forename: Gomathinayagam
authors.initials: G
authors.lastname: Sinnathamby
authors.forename: Takuya
authors.initials: T
authors.lastname: Osada
authors.forename: Julie
authors.initials: J
authors.lastname: Hafner
authors.forename: Mohan
authors.initials: M
authors.lastname: Philip
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Clay
authors.forename: H Kim
authors.initials: HK
authors.lastname: Lyerly
authors.forename: Ramila
authors.initials: R
authors.lastname: Philip
mesh_terms: D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000302:isolation & purification*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I