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Clin Cancer Res. 2006 May 15;12(10):3130-6.

Detection and functional analysis of CD8+ T cells specific for PRAME: a target for T-cell therapy.

Author information

1
Department of Clinical Oncology, Leiden University Medical Center, Leiden, Netherlands. M.Griffioen@lumc.nl

Abstract

PURPOSE:

Preferentially expressed antigen on melanomas (PRAME) is an interesting antigen for T-cell therapy because it is frequently expressed in melanomas (95%) and other tumor types. Moreover, due to its role in oncogenic transformation, PRAME-negative tumor cells are not expected to easily arise and escape from T-cell immunity. The purpose of this study is to investigate the usefulness of PRAME as target for anticancer T-cell therapies.

EXPERIMENTAL DESIGN:

HLA-A*0201-subtyped healthy individuals and advanced melanoma patients were screened for CD8+ T cells directed against previously identified HLA-A*0201-binding PRAME peptides by IFN-gamma enzyme-linked immunosorbent spot assays and tetramer staining. PRAME-specific T-cell clones were isolated and tested for recognition of melanoma and acute lymphoid leukemia (ALL) cell lines. PRAME mRNA expression was determined by quantitative real-time reverse transcription-PCR.

RESULTS:

In 30% to 40% of healthy individuals and patients, PRA(100-108)-specific CD8+ T cells were detected both after in vitro stimulation and directly ex vivo after isolation by magnetic microbeads. Although CD45RA- memory PRA(100-108)-specific T cells were found in some individuals, the majority of PRA(100-108)-tetramer+ T cells expressed CD45RA, suggesting a naive phenotype. PRA(100-108)-tetramer+ T-cell clones were shown to recognize and lyse HLA-A*0201+ and PRAME+ melanoma but not ALL cell lines. Quantitative real-time reverse transcription-PCR showed significantly lower PRAME mRNA levels in ALL than in melanoma cell lines, suggesting that PRAME expression in ALL is below the recognition threshold of our PRA(100-108)-tetramer+ T cells.

CONCLUSION:

These data support the usefulness of PRAME and in particular the PRA(100-108) epitope as target for T-cell therapy of PRAME-overexpressing cancers.

PMID:
16707612
DOI:
10.1158/1078-0432.CCR-05-2578
[Indexed for MEDLINE]
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