title: Phase I dendritic cell p53 peptide vaccine for head and neck cancer.
abstract: BACKGROUND
  p53 accumulation in head and neck squamous cell carcinoma (HNSCC) cells creates a targetable tumor antigen. Adjuvant dendritic cell (DC)-based vaccination against p53 was tested in a phase I clinical trial.
  
  
  METHODS
  Monocyte-derived DC from 16 patients were loaded with two modified HLA-class I p53 peptides (Arm 1), additional Th tetanus toxoid peptide (Arm 2), or additional Th wild-type (wt) p53-specific peptide (Arm 3). Vaccine DCs (vDC) were delivered to inguinal lymph nodes at three time points. vDC phenotype, circulating p53-specific T cells, and regulatory T cells (Treg) were serially monitored by flow cytometry and cytokine production by Luminex. vDC properties were compared with those of DC1 generated with an alternative maturation regimen.
  
  
  RESULTS
  No grade II-IV adverse events were observed. Two-year disease-free survival of 88% was favorable. p53-specific T-cell frequencies were increased postvaccination in 11 of 16 patients (69%), with IFN-γ secretion detected in four of 16 patients. Treg frequencies were consistently decreased (P = 0.006) relative to prevaccination values. The phenotype and function of DC1 were improved relative to vDC.
  
  
  CONCLUSIONS
  Adjuvant p53-specific vaccination of patients with HNSCC was safe and associated with promising clinical outcome, decreased Treg levels, and modest vaccine-specific immunity. HNSCC patients' DC required stronger maturation stimuli to reverse immune suppression and improve vaccine efficacy.
authors.affiliation: Authors' Affiliations: Cancer Immunology Program; Biostatistics Facility, University of Pittsburgh Cancer Institute; Departments of Pathology and Otolaryngology, University of Pittsburgh School of Medicine; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Medicine, Hematology/Oncology, University of Texas-San Antonio Cancer Center, San Antonio, Texas; and Department of Otolaryngology, University of Ulm, Germany.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Schuler
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Harasymczuk
authors.forename: Carmen
authors.initials: C
authors.lastname: Visus
authors.forename: Albert
authors.initials: A
authors.lastname: Deleo
authors.forename: Sumita
authors.initials: S
authors.lastname: Trivedi
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
authors.forename: William
authors.initials: W
authors.lastname: Gooding
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Butterfield
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy / Q000009:adverse effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000276:immunology*; D010641:Phenotype; D000077195:Squamous Cell Carcinoma of Head and Neck; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000276:immunology*; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53