T-cell responses against tyrosinase 368-376(370D) peptide in HLA*A0201+ melanoma patients: randomized trial comparing incomplete Freund's adjuvant, granulocyte macrophage colony-stimulating factor, and QS-21 as immunological adjuvants

Clin Cancer Res. 2002 May;8(5):967-72.


We conducted a randomized trial in HLA*A0201+ patientswith American Joint Committee on Cancer stage III or IV melanoma immunized with tyrosinase 368-376(370D) peptide and gp100 209-217(210M) peptide to compare the potency of three different adjuvants. Patients received 3 monthly immunizations with 500 microg of each peptide either with incomplete Freund's adjuvant (IFA), QS-21, or granulocyte macrophage colony-stimulating factor (GM-CSF). The primary end point was induction of IFN-gamma release by CD8+ T cells against tyrosinase and gp100 peptides measured by enzyme-linked immunospot assays without in vitro prestimulation measured pretreatment, 2 and 8 weeks after the third vaccination. Four of 9 and 4 of 8 patients immunized using QS-21 and GM-CSF, respectively, developed increased frequencies of CD8+ T cells against tyrosinase 370D peptide compared with 0 of 9 patients immunized using IFA (P = 0.045). T-cell responses against a gp100-related peptide showed similar results, but their relevance to T-cell reactivity against native gp100 209-217 is uncertain. These results show that: (a) QS-21 and GM-CSF are superior to IFA as immunological adjuvants for vaccination against tyrosinase 370D peptide; and (b) with appropriate adjuvants, increased frequencies of peptide-specific T cells after vaccination can be detected by enzyme-linked immunospot without prolonged prestimulation in vitro.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Freund's Adjuvant / administration & dosage
  • Freund's Adjuvant / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • HLA-A2 Antigen / immunology*
  • Humans
  • Lymphocyte Count
  • Male
  • Melanoma / drug therapy
  • Melanoma / immunology*
  • Middle Aged
  • Monophenol Monooxygenase / administration & dosage
  • Monophenol Monooxygenase / chemistry
  • Monophenol Monooxygenase / immunology*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Saponins / administration & dosage
  • Saponins / immunology
  • T-Lymphocytes / immunology*
  • Treatment Outcome
  • Vaccination


  • HLA-A2 Antigen
  • Peptide Fragments
  • Saponins
  • saponin QA-21V1
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Freund's Adjuvant
  • Monophenol Monooxygenase