Characterization of long-term effector-memory T-cell responses in patients with resected high-risk melanoma receiving a melanoma Peptide vaccine.
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| Abstract |
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.
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| Authors | Brian Chiong, Raymond Wong, Peter Lee, Joan Delto, Ronald Scotland, Roy Lau, Jeffrey Weber |
| Journal | Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2004 Sep-Oct Vol. 27 Issue 5 Pg. 368-79 ISSN: 1524-9557 [Print] United States |
| PMID | 15314545 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.) |
| Copyright | Copyright 2004 Lippincott Williams & Wilkins |
| Chemical References |
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