Activation of human melanoma reactive CD8+ T cells by vaccination with an immunogenic peptide analog derived from Melan-A/melanoma antigen recognized by T cells-1.
OBJECTIVE
As compared with natural tumor peptide sequences, carefully selected analog peptides may be more immunogenic and thus better suited for vaccination. However, T cells in vivo activated by such altered analog peptides may not necessarily be tumor specific because sequence and structure of peptide analogs differ from corresponding natural peptides.


METHODS
Three melanoma patients were immunized with a Melan-A peptide analog that binds more strongly to HLA-A*0201 and is more immunogenic than the natural sequence. This peptide was injected together with a saponin-based adjuvant, followed by surgical removal of lymph node(s) draining the site of vaccination.


RESULTS
Ex vivo analysis of vaccine site draining lymph nodes revealed antigen-specific CD8+ T cells, which had differentiated to memory cells. In vitro, these cells showed accelerated proliferation upon peptide stimulation. Nearly all (16 of 17) of Melan-A-specific CD8+ T-cell clones generated from these lymph nodes efficiently killed melanoma cells.


CONCLUSIONS
Patient immunization with the analog peptide leads to in vivo activation of T cells that were specific for the natural tumor antigen, demonstrating the usefulness of the analog peptide for melanoma immunotherapy.
Ayyoub
Maha
M
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, CH-1005 Lausanne, Switzerland.
Zippelius
Alfred
A
Pittet
Mikaël J
MJ
Rimoldi
Donata
D
Valmori
Danila
D
Cerottini
Jean-Charles
JC
Romero
Pedro
P
Lejeune
Ferdy
F
Liénard
Danielle
D
Speiser
Daniel E
DE
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000276:immunology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments