Induction of circulating tumor-reactive CD8+ T cells after vaccination of melanoma patients with the gp100209-2M peptide

Sybren L. Meijer, Annemieke Dols, Shawn M. Jensen, Hong-Ming Hu, William Miller, Edwin Walker, Pedro Romero, Bernard A. Fox, Walter J. Urba*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Patients with stage I-III melanoma were vaccinated with the modified HLA-A2-binding gp100209-2M-peptide after complete surgical resection of their primary lesion and sentinel node biopsy. Cytoplasmic interferon-γ 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 gp100209-217 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.

Original languageEnglish
Pages (from-to)533-543
Number of pages11
JournalJournal of Immunotherapy
Volume30
Issue number5
DOIs
Publication statusPublished - 1 Jul 2007
Externally publishedYes

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