title: Ex vivo detectable activation of Melan-A-specific T cells correlating with inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA.
abstract: The purpose of this study was to test melanoma vaccines consisting of peptides and immunological adjuvants for optimal immunogenicity and to evaluate laboratory immune monitoring for in vivo relevance. Forty-nine HLA-A2 positive patients with Melan-A positive melanoma were repeatedly vaccinated with Melan-A peptide, with or without immune adjuvant AS02B (QS21 and MPL) or IFA. Peptide-specific CD8 T cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers and IFN-gamma ELISPOT assays. The vaccines were well tolerated. In vivo expansion of Melan-A-specific CD8 T cells was observed in 13 patients (1/12 after vaccination with peptide in AS02B and 12/17 after vaccination with peptide in IFA). The T cells produced IFN-gamma and downregulated CD45RA and CD28. T-cell responses correlated with inflammatory skin reactions at vaccine injection sites (P < 0.001) and with DTH reaction to Melan-A peptide (P < 0.01). Twenty-six of 32 evaluable patients showed progressive disease, whereas 4 patients had stable disease. The two patients with the strongest Melan-A-specific T-cell responses experienced regression of metastases in skin, lymph nodes, and lung. We conclude that repeated vaccination with Melan-A peptide in IFA frequently leads to sustained responses of specific CD8 T cells that are detectable ex vivo and correlate with inflammatory skin reactions.
authors.affiliation: Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Danielle
authors.initials: D
authors.lastname: Liénard
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Marie
authors.initials: M
authors.lastname: Marchand
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dietrich
authors.forename: Nicolas
authors.initials: N
authors.lastname: van Baren
authors.forename: Christine
authors.initials: C
authors.lastname: Geldhof
authors.forename: Pascal
authors.initials: P
authors.lastname: Batard
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.forename: Mikaël J
authors.initials: MJ
authors.lastname: Pittet
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
authors.forename: Katharina
authors.initials: K
authors.lastname: Fleischhauer
authors.forename: Ferdy
authors.initials: F
authors.lastname: Lejeune
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000633:toxicity; D003872:Dermatitis / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005620:Freund's Adjuvant / Q000627:therapeutic use; D006801:Humans; D008055:Lipids / Q000627:therapeutic use; D008213:Lymphocyte Activation; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009363:Neoplasm Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D008055:Lipids; C031540:M-protein, influenza virus; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010455:Peptides; D014763:Viral Matrix Proteins; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant