title: A melanoma helper peptide vaccine increases Th1 cytokine production by leukocytes in peripheral blood and immunized lymph nodes.
abstract: BACKGROUND
  Cancers produce soluble and cell-associated molecules that can suppress or alter antitumor immunity. Preclinical studies suggest the disease burden may alter the cytokine profile of helper T cell responses to cancer antigens. We studied cytokine production by helper T cells responding to vaccination with 6 melanoma helper peptides (6MHP) in blood and lymph nodes.
  
  
  METHODS
  Twenty-three patients with stage IIIB-IV melanoma received a 6MHP vaccine. Antigen-reactive T cells from blood and draining lymph nodes were cultured, exposed to antigen, and then supernatants (days 2 and 5) were assayed for Th1 and Th2 cytokines. Results from 4 time points were compared to pre-vaccine levels.
  
  
  RESULTS
  Cytokine responses to vaccinating peptides were observed in 83% of patients. Th1 favoring responses were most common (17 of 19 responders). The most abundant cytokines produced were IFN-γ and IL-5 in the PBMC's. IL-2 responses predominated in cells obtained from draining lymph nodes in 2-day culture but not in 5-day cultures. Patients with clinically measurable disease produced similar levels of total cytokine and similar degree of Th1 polarization as patients with no evidence of disease (NED).
  
  
  CONCLUSIONS
  The MHC class II-associated peptides used in this study induced helper T cells with a Th1-biased cytokine response in both PBMC and sentinel immunized nodes. Most patients can mount a Th1 dominant response to these peptides. Future studies are needed to test newer vaccine adjuvants in combination with these peptides.
  
  
  BACKGROUND
  CDR0000378171, Clinicaltrials: NCT00089219.
authors.affiliation: Department of Medicine/Division of Hematology-Oncology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Dillon
authors.affiliation: Department of Surgery/Division of Surgical Oncology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Olson
authors.affiliation: Cancer Center, Charlottesville, VA 22908, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Czarkowski
authors.affiliation: Department of Public Health Sciences, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Gina R
authors.initials: GR
authors.lastname: Petroni
authors.affiliation: Department of Public Health Sciences, University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Smolkin
authors.affiliation: Department of Medicine/Division of Hematology-Oncology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Grosh
authors.affiliation: Department of Surgery/Division of Surgical Oncology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Chianese-Bullock
authors.affiliation: Department of Surgery/Division of Surgical Oncology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Donna H
authors.initials: DH
authors.lastname: Deacon
authors.affiliation: Department of Surgery/Division of Surgical Oncology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Slingluff
keywords: Antigens; Cytokines; Cytotoxic; Human; Immunotherapy; Melanoma/im; Neoplasm; T-Lymphocytes; Tumor vaccines