Ex vivo detectable activation of Melan-A-specific T cells correlating with inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA.
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.
Liénard
Danielle
D
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Rimoldi
Donata
D
Marchand
Marie
M
Dietrich
Pierre-Yves
PY
van Baren
Nicolas
N
Geldhof
Christine
C
Batard
Pascal
P
Guillaume
Philippe
P
Ayyoub
Maha
M
Pittet
Mikaël J
MJ
Zippelius
Alfred
A
Fleischhauer
Katharina
K
Lejeune
Ferdy
F
Cerottini
Jean-Charles
JC
Romero
Pedro
P
Speiser
Daniel E
DE
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
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