In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 12, No. 10 ( 2006-05-15), p. 3130-3136
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-γ 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, PRA100-108-specific CD8+ T cells were detected both after in vitro stimulation and directly ex vivo after isolation by magnetic microbeads. Although CD45RA− memory PRA100-108-specific T cells were found in some individuals, the majority of PRA100-108-tetramer+ T cells expressed CD45RA, suggesting a naive phenotype. PRA100-108-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 PRA100-108-tetramer+ T cells. Conclusion: These data support the usefulness of PRAME and in particular the PRA100-108 epitope as target for T-cell therapy of PRAME-overexpressing cancers.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-05-2578
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2006
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
