Characterization of antigen-specific CD8+ T lymphocyte responses in skin and peripheral blood following intradermal peptide vaccination

Qiyuan Chen, Heather Jackson, Mark Shackleton, Phillip Parente, Wendie Hopkins, Sue Sturrock, Duncan MacGregor, Eugene Maraskovsky, Tsin Yee Tai, Nektaria Dimopoulos, Kelly Anne Masterman, Tina Luke, Ian D. Davis, Weisan Chen, Jonathan Cebon

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34 Citations (Scopus)

Abstract

Immune responses to cancer vaccines are commonly tested by measuring cutaneous reactions to intradermal (i.d.) antigen. When well-characterized peptide epitopes are injected i.d., infiltrates of CD4+ and CD8+ T lymphocytes are frequently seen. In this study, we have further characterized T cells derived from vaccine-infiltrating lymphocyte (VIL) responses. We found that the infiltrates capable of producing IFN-gamma and cytolytic activity could recognize vaccine peptide, as well as antigen-positive melanoma cells. We studied antigen-specific T cell responses from VILs and peripheral blood in 10 patients who participated in a clinical trial. All patients received systemic Flt3 ligand (20 μg/kg/d) and i.d. peptides: Three NY-ESO-1 peptides, SLLMWITQCFL (157-167), SLLMWITQC (157-165), QLSLLMWIT (155-163); tyrosinase internal peptide YMDGTMSQV (368-376); Melan-A/MART-1 analogue peptide ELAGIGILTV (26-35, E27L substitution); and influenza matrix peptide GILGFVFTL (58-66). In 54 paired VIL and peripheral blood analyses, a good correlation was found between responses in skin and in blood. These cells could be rapidly expanded in a short-term assay and thus appear to be memory T cells. The demonstrated presence of antigen-specific T cells at vaccination sites validates this method of assessing the immune response to i.d. vaccines.

Original languageEnglish
Article number5
JournalCancer Immunity
Volume5
Publication statusPublished - 9 Mar 2005

Keywords

  • Clinical trial
  • Immunological monitoring
  • Melanoma
  • Peptides
  • Vaccination

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