title: Immunologic and clinical outcomes of vaccination with a multiepitope melanoma peptide vaccine plus low-dose interleukin-2 administered either concurrently or on a delayed schedule.
abstract: OBJECTIVE
  A phase II trial was performed to test whether systemic low-dose interleukin-2 (IL-2) augments T-cell immune responses to a multipeptide melanoma vaccine. Forty patients with resected stage IIB-IV melanoma were randomly assigned to vaccination with four gp100- and tyrosinase-derived peptides restricted by human leukocyte antigen (HLA) -A1, HLA-A2, and HLA-A3, and a tetanus helper peptide plus IL-2 administered daily either beginning day 7 (group 1), or beginning day 28 (group 2).
  
  
  METHODS
  T-cell responses were assessed by an interferon gamma ELIspot assay in peripheral blood lymphocytes (PBL) and in a lymph node draining a vaccination site (sentinel immunized node [SIN]). Patients were followed for disease-free and overall survival.
  
  
  RESULTS
  T-cell responses to the melanoma peptides were observed in 37% of PBL and 38% of SINs in group 1, and in 53% of PBL and 83% of SINs in group 2. The magnitude of T-cell response was higher in group 2. The tyrosinase peptides DAEKSDICTDEY and YMDGTMSQV were more immunogenic than the gp100 peptides YLEPGPVTA and ALLAVGATK. T-cell responses were detected in the SINs more frequently, and with higher magnitude, than responses in the PBL. Disease-free survival estimates at 2 years were 39% (95% CI, 18% to 61%) for group 1, and 50% (95% CI, 28% to 72%) for group 2 (P = .32).
  
  
  CONCLUSIONS
  The results of this study support the safety and immunogenicity of a vaccine composed of four peptides derived from gp100 and tyrosinase. The low-dose IL-2 regimen used for group 1 paradoxically diminishes the magnitude and frequency of cytotoxic T lymphocyte responses to these peptides.
authors.affiliation: Department of Surgery, Human Immune Therapy Center, University of Virginia Health System, Charlottesville, VA 22908, USA. cls8h@virginia.edu
authors.forename: Craig L
authors.initials: CL
authors.lastname: Slingluff
authors.forename: Gina R
authors.initials: GR
authors.lastname: Petroni
authors.forename: Galina V
authors.initials: GV
authors.lastname: Yamshchikov
authors.forename: Sarah
authors.initials: S
authors.lastname: Hibbitts
authors.forename: William W
authors.initials: WW
authors.lastname: Grosh
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Chianese-Bullock
authors.forename: Eric A
authors.initials: EA
authors.lastname: Bissonette
authors.forename: Donna L
authors.initials: DL
authors.lastname: Barnd
authors.forename: Donna H
authors.initials: DH
authors.lastname: Deacon
authors.forename: James W
authors.initials: JW
authors.lastname: Patterson
authors.forename: Jayashree
authors.initials: J
authors.lastname: Parekh
authors.forename: Patrice Y
authors.initials: PY
authors.lastname: Neese
authors.forename: Elizabeth M H
authors.initials: EM
authors.lastname: Woodson
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Wiernasz
authors.forename: Priscilla
authors.initials: P
authors.lastname: Merrill
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome; D014443:Tyrosine / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D058951:gp100 Melanoma Antigen
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D006680:HLA Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D022223:Vaccines, Subunit; D058951:gp100 Melanoma Antigen; D014443:Tyrosine