Immune responses to a class II helper peptide epitope in patients with stage III/IV resected melanoma.
The importance of CD8(+) cytolytic T cells for protection from viral infection and in the generation of immune responses against tumors has been well established. In contrast, the role of CD4(+) T-helper cells in human infection and in cancer immunity has yet to be clearly defined. In this pilot study, we show that immunization of three resected, high-risk metastatic melanoma patients with a T-helper epitope derived from the melanoma differentiation antigen, melanoma antigen recognized by T cells-1, results in CD4(+) T-cell immune responses. Immune reactivity to that epitope was detected by DR4-peptide tetramer staining, and enzyme-linked immunospot assay of fresh and restimulated CD4(+) T cells from patients over the course of the 12-month vaccine regimen. The postvaccine CD4(+) T cells exhibited a mixed T-helper 1/T-helper 2 phenotype, proliferated in response to the antigen and promiscuously recognized the peptide epitope bound to different human leukocyte antigen-DRbeta alleles. For 1 DRbeta1*0401(+) patient, antigen-specific CD4(+) T cells recognized human leukocyte antigen-matched antigen-expressing tumor cells, secreted granzyme B, and also exhibited cytolysis that was MHC class II-restricted. These data establish the immunogenicity of a class II epitope derived from a melanoma-associated antigen and support the inclusion of class II peptides in future melanoma vaccine therapies.
Department of Medicine, Keck/University of Southern California School of Medicine, Los Angeles, California 90089, USA.
Raymond
R
Wong
Roy
R
Lau
Jenny
J
Chang
Tina
T
Kuus-Reichel
Vincent
V
Brichard
Claudine
C
Bruck
Jeffrey
J
Weber
D000367:Age Factors; D000483:Alleles; D000951:Antigens, Neoplasm; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes; D006680:HLA Antigens / Q000737:chemistry; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000601:surgery* / Q000628:therapy*; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010865:Pilot Projects; D012503:Saponins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015704:CD4 Antigens; D019496:Cancer Vaccines; D000939:Epitopes; D006680:HLA Antigens; D006684:HLA-DR Antigens; D008050:Lipid A; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010455:Peptides; D012503:Saponins; C078785:saponin QA-21V1; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C048436:monophosphoryl lipid A