High-avidity cytotoxic T lymphocytes specific for a new PRAME-derived peptide can target leukemic and leukemic-precursor cells

Blood. 2011 Mar 24;117(12):3353-62. doi: 10.1182/blood-2010-08-300376. Epub 2011 Jan 28.


The cancer testis antigen (CTA) preferentially expressed antigen of melanoma (PRAME) is overexpressed by many hematologic malignancies, but is absent on normal tissues, including hematopoietic progenitor cells, and may therefore be an appropriate candidate for T cell-mediated immunotherapy. Because it is likely that an effective antitumor response will require high-avidity, PRAME-specific cytotoxic T lymphocytes (CTLs), we attempted to generate such CTLs using professional and artificial antigen-presenting cells loaded with a peptide library spanning the entire PRAME protein and consisting of 125 synthetic pentadecapeptides overlapping by 11 amino acids. We successfully generated polyclonal, PRAME-specific CTL lines and elicited high-avidity CTLs, with a high proportion of cells recognizing a previously uninvestigated HLA-A*02-restricted epitope, P435-9mer (NLTHVLYPV). These PRAME-CTLs could be generated both from normal donors and from subjects with PRAME(+) hematologic malignancies. The cytotoxic activity of our PRAME-specific CTLs was directed not only against leukemic blasts, but also against leukemic progenitor cells as assessed by colony-forming-inhibition assays, which have been implicated in leukemia relapse. These PRAME-directed CTLs did not affect normal hematopoietic progenitors, indicating that this approach may be of value for immunotherapy of PRAME(+) hematologic malignancies.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Blood Donors
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / immunology
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism
  • HLA-A Antigens / metabolism
  • HLA-A2 Antigen
  • Humans
  • K562 Cells
  • Leukemia / genetics
  • Leukemia / immunology*
  • Leukemia / pathology
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • T-Cell Antigen Receptor Specificity* / immunology
  • T-Cell Antigen Receptor Specificity* / physiology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*


  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A*02 antigen
  • HLA-A2 Antigen
  • PRAME protein, human
  • Peptide Fragments