Ex vivo characterization of polyclonal memory CD8 + T-cell responses to PRAME-specific peptides in patients with acute lymphoblastic leukemia and acute and chronic myeloid leukemia

Katayoun Rezvani, Agnes S M Yong, Abdul Tawab, Behnam Jafarpour, Rhoda Eniafe, Stephan Mielke, Bipin N. Savani, Keyvan Keyvanfar, Yixin Li, Roger Kurlander, A. John Barrett

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91 Citations (Scopus)

Abstract

Preferentially expressed antigen of melanoma (PRAME) is aberrantly expressed in hematologic malignancies and may be a useful target for immunotherapy in leukemia. To determine whether PRAME is naturally immunogenic, we studied CD8 +T-cell responses to 4 HLA-A*0201-restricted PRAME-derived epitopes (PRA100, PRA142, PRA300, PRA425) in HLA-A*0201- positive patients with acute lymphoblastic leukemia (ALL), acute my-eloid leukemia (AML), chronic myeloid leukemia (CML), and healthy donors. CD8 +T cells recognizing PRAME peptides could be detected ex vivo in 4 of 10 ALL, 6 of 10 AML, 3 of 10 CML patients, and 3 of 10 donors by HLA-A2 tetramer analysis and flow cytometry for intracellular interferon-γ. The frequency of PRAME-specific CD8 + T cells was greater in patients with AML, CML, and ALL than healthy controls. All peptides were immu-nogenic in patients, while responses were only detected to PRA300 in donors. High PRAME expression in patient peripheral blood mononuclear cells was associated with responses to greater than or equal to 2 PRAME epitopes compared with low.PRAME expression levels (4/7 vs 0/23, P =.001), suggesting a PRAME-driven T-cell response. PRAME-specific T cells were readily expanded in short-term cultures in donors and patients. These results provide evidence for spontaneous T cell reactivity against multiple epitopes of PRAME in ALL, AML, and CML. The potential for developing PRAME as a target for immunotherapy in leukemia deserves further exploration. copyright 2007 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)2245-2255
Number of pages11
JournalBlood
Volume113
Issue number10
DOIs
Publication statusPublished - 5 Mar 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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