title: Induction of circulating tumor-reactive CD8+ T cells after vaccination of melanoma patients with the gp100 209-2M peptide.
abstract: Patients with stage I-III melanoma were vaccinated with the modified HLA-A2-binding gp100(209-2M)-peptide after complete surgical resection of their primary lesion and sentinel node biopsy. Cytoplasmic interferon-gamma production by freshly thawed peripheral blood mononuclear cells (direct ex vivo analysis) or by peripheral blood mononuclear cells subjected to 1 cycle of in vitro sensitization with peptide, interleukin-2, and interleukin-15 was measured following restimulation with the modified and native gp100 peptides, and also A2gp100 melanoma cell lines. Peptide-reactive and tumor-reactive T cells were detected in 79% and 66% of selected patients, respectively. Patients could be classified into 3 groups according to their vaccine-elicited T-cell responses. One group of patients responded only to the modified peptide used for immunization, whereas another group of patients reacted to both the modified and native gp100 peptides, but not to naturally processed gp100 antigen on melanoma cells. In the third group of patients, circulating CD8 T cells recognized A2gp100 melanoma cell lines and also both the modified and native peptides. T cells with a low functional avidity, which were capable of lysing tumor cells only if tumor cells were first pulsed by the exogenous administration of native gp100(209-217) peptide were identified in most patients. These results indicate that vaccination with a modified gp100 peptide induced a heterogeneous group of gp100-specific T cells with a spectrum of functional avidities; however, high avidity, tumor-reactive T cells were detected in the majority of patients.
authors.affiliation: Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan Street, Portland, OR 97213, USA.
authors.forename: Sybren L
authors.initials: SL
authors.lastname: Meijer
authors.forename: Annemieke
authors.initials: A
authors.lastname: Dols
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Jensen
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Hu
authors.forename: William
authors.initials: W
authors.lastname: Miller
authors.forename: Edwin
authors.initials: E
authors.lastname: Walker
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Fox
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma