In vivo activation of melanoma-specific CD8(+) T cells by endogenous tumor antigen and peptide vaccines. A comparison to virus-specific T cells.
Many new types of vaccines against infectious or malignant diseases are currently being proposed. Careful characterization of the induced immune response is required in assessing their efficiency. While in most studies human tumor antigen-specific T cells are analyzed after in vitro re-stimulation, we investigated these T cells directly ex vivo using fluorescent tetramers. In peripheral blood lymphocytes from untreated melanoma patients with advanced disease, a fraction of tumor antigen (Melan-A/MART-1)-specific T cells were non-naive, thus revealing tumor-driven immune activation. After immunotherapy with synthetic peptides plus adjuvant, we detected tumor antigen-specific T cells that proliferated and differentiated to memory cells in vivo in some melanoma patients. However, these cells did not present the features of effector cells as found in cytomegalovirus specific T cells analyzed in parallel. Thus, peptide plus adjuvant vaccines can lead to activation and expansion of antigen specific CD8(+) T cells in PBL. Differentiation to protective CD8(+) effector cells may, however, require additional vaccine components that stimulate T cells more efficiently, a major challenge for the development of future immunotherapy.
Speiser
Daniel E
DE
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital (CHUV), Lausanne, Switzerland. daniel.speiser@hospvd.ch
Liénard
Danielle
D
Pittet
Mikaël J
MJ
Batard
Pascal
P
Rimoldi
Donata
D
Guillaume
Philippe
P
Cerottini
Jean-Charles
JC
Romero
Pedro
P
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D002454:Cell Differentiation; D003587:Cytomegalovirus / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D058965:MART-1 Antigen; D008353:Mannitol / Q000031:analogs & derivatives*; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009363:Neoplasm Proteins / Q000276:immunology*; D009829:Oleic Acids; D010446:Peptide Fragments / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use; D014763:Viral Matrix Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D009829:Oleic Acids; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D014763:Viral Matrix Proteins; C098952:influenza virus membrane protein (58-66); C001681:mannide monooleate; D008353:Mannitol