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 Journal Article


Authors: Schaed, S. G.; Klimek, V. M.; Panageas, K. S.; Musselli, C. M.; Butterworth, L.; Hwu, W. J.; Livingston, P. O.; Williams, L.; Lewis, J. J.; Houghton, A. N.; Chapman, P. B.
Article Title: 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
Abstract: We conducted a randomized trial in HLA*A0201+ patients with 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 μg 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-γ 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 of 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.
Keywords: adult; clinical article; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; unclassified drug; clinical trial; cd8 antigen; cd8-positive t-lymphocytes; t-lymphocytes; glycoprotein gp 100; melanoma; controlled clinical trial; randomized controlled trial; granulocyte macrophage colony stimulating factor; cell differentiation; antineoplastic activity; enzyme linked immunosorbent assay; immune response; gamma interferon; immunogenicity; peptide fragments; vaccination; cytotoxic t lymphocyte; autoimmunity; monophenol monooxygenase; hla a antigen; tyrosinase related protein 1; antigen presenting cell; t lymphocyte activation; lymphocyte count; saponins; hla-a2 antigen; qs 21; granulocyte-macrophage colony-stimulating factor; freund's adjuvant; freund adjuvant; humans; human; male; female; priority journal; article; tyrosinase[368-376] peptide
Journal Title: Clinical Cancer Research
Volume: 8
Issue: 5
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2002-05-01
Start Page: 967
End Page: 972
Language: English
PUBMED: 12006508
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus