Characterization of long-term effector-memory T-cell responses in patients with resected high-risk melanoma receiving a melanoma Peptide vaccine.
The authors determined whether long-term memory T cells could be detected in patients who received a multipeptide vaccine for high-risk resected melanoma. Five HLA-A*0201 patients received a vaccine that included the gp100(209-217) (210M) peptide with Montanide ISA 51. Peripheral blood mononuclear cells were obtained before therapy, after 6 months of vaccinations, and from 18 months to 36 months later. The presence of gp100 antigen-specific cytolytic T cells was measured by ELISPOT, tetramer and chromium release assays. Tetramer-positive CD8 cells were phenotyped by flow cytometry for markers including CD44, CD45RA, and CCR7. T-cell avidity and its evolution over time were examined in selected patients. Epitope spreading was analyzed by assessment of gp100(280-288) (288V) T cells. All patients exhibited a significant increase in tetramer-positive gp100-specific CD8 T cells that decayed at different rates over 18 to 36 months after vaccinations. Cells from all patients exhibited an effector-memory phenotype and were generally CD45 RA low/CCR7 negative and CD44 positive. Tetramer-positive cells declined over time in four of the five patients, but the proportion of tetramer-positive CD8 cells that secreted gamma-interferon rose, suggesting enrichment for effector cells. Epitope spreading for the gp100(280-288) (288V) epitope was detected. One patient maintained a population of 2.5% circulating gp100 tetramer-positive cells over 36 months. Avidity analysis showed no changes over time after induction of antigen-specific T cells. Vaccination with a heteroclitic melanoma antigen peptide with Montanide ISA 51 generated populations of circulating functional effector-memory T cells that were specific for gp100 and long-lived in the circulation for periods of 18 to 36 months after vaccination.
Department of Medicine and Molecular Microbiology/Immunology, Keck-University of Southern California School of Medicine, Los Angeles, California 90089, USA.
Brian
B
Chiong
Raymond
R
Wong
Peter
P
Lee
Joan
J
Delto
Ronald
R
Scotland
Roy
R
Lau
Jeffrey
J
Weber
D000328:Adult; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D002986:Clinical Trials as Topic; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008353:Mannitol / Q000031:analogs & derivatives* / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009829:Oleic Acids / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D010455:Peptides; D010641:Phenotype; D013997:Time Factors; D058951:gp100 Melanoma Antigen
D015415:Biomarkers; D019496:Cancer Vaccines; D000939:Epitopes; D008562:Membrane Glycoproteins; D009829:Oleic Acids; C548637:PMEL protein, human; D010446:Peptide Fragments; D010455:Peptides; D058951:gp100 Melanoma Antigen; C548641:gp100(280-288) melanoma antigen peptide; C477385:montanide ISA 51; D008353:Mannitol; D007371:Interferon-gamma