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	Cancer Immunity, Vol. 5, p. 5 (9 March 2005) Submitted: 9 September 2004. Accepted: 24 December 2004. Communicated by: HF Oettgen Characterization of antigen-specific CD8+ T lymphocyte responses in skin and peripheral blood following intradermal peptide vaccination Qiyuan Chen1, Heather Jackson1, Mark Shackleton1,2*, Phillip Parente1,2, Wendie Hopkins1, Sue Sturrock2, Duncan MacGregor2, Eugene Maraskovsky1, Tsin Yee Tai1, Nektaria Dimopoulos1, Kelly-Anne Masterman1, Tina Luke1, Ian D. Davis1,2, Weisan Chen1, and Jonathan Cebon1,2 1Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia 2Austin Hospital, Heidelberg, Victoria, Australia *Present address: The Walter and Eliza Hall Institute of Medical Research (WEHI) , Victoria, Australia Keywords: clinical trial, melanoma, vaccination, peptides, immunological monitoring

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.