Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy

Willemijn van den Ancker, Jurjen M. Ruben, Theresia M. Westers, Dewi Wulandari, Hetty J. Bontkes, Erik Hooijberg, Anita G.M. Stam, Saskia J.A.M. Santegoets, Gert J. Ossenkoppele, Tanja de Gruijl, Arjan Van de Loosdrecht

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15 Citations (Scopus)

Abstract

Active immunotherapy may prevent the relapse of acute myeloid leukemia (AML) by inducing leukemia-specific T cells. Here, we investigated whether Wilms' tumor 1 (WT1) and preferentially expressed antigen in melanoma (PR AME)-specific T cells could be induced upon the priming of healthy donor- and AML patient-derived T cells with HLA-A2-matched, peptide-loaded allogeneic dendritic cells. AML-reactive, tetramer (Tm)-binding and interferon-producing, cytotoxic T lymphocytes specific for PR AME could readily be isolated from healthy individuals and maintained in culture. In this setting, priming efficacy was significantly higher for PR AME than for WT1. The priming of T cells from patient-derived material proved to be near-to-impossible: No leukemia-associated antigen (LAA)-specific T cell could be primed in 4 patients that had recently achieved a complete response (CR), and in only 1 out of 3 patients exhibiting a sustained CR we did observe WT1-specific T cells, though with a low frequency. These findings suggest that the functionality and/or repertoire of T cells differ in healthy subjects and AML patients in CR, and may have repercussions for the implementation of active vaccination approaches against AML.

Original languageEnglish
Article numbere23971
JournalOncoImmunology
Volume2
Issue number4
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Acute myeloid leukemia
  • Dendritic cell-based vaccination
  • Immunotherapy
  • PRAME
  • T- cell priming
  • WT1

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