title: Priming of PRAME- and WT1-specific CD8+T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy.
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 (PRAME)-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 PRAME could readily be isolated from healthy individuals and maintained in culture. In this setting, priming efficacy was significantly higher for PRAME 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.
authors.affiliation: Department of Hematology; VU University Medical Center/Cancer Center Amsterdam; Amsterdam, The Netherlands.
authors.forename: Willemijn
authors.initials: W
authors.lastname: van den Ancker
authors.forename: Jurjen M
authors.initials: JM
authors.lastname: Ruben
authors.forename: Theresia M
authors.initials: TM
authors.lastname: Westers
authors.forename: Dewi
authors.initials: D
authors.lastname: Wulandari
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
authors.forename: Erik
authors.initials: E
authors.lastname: Hooijberg
authors.forename: Anita G M
authors.initials: AG
authors.lastname: Stam
authors.forename: Saskia J A M
authors.initials: SJ
authors.lastname: Santegoets
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Tanja
authors.initials: T
authors.lastname: de Gruijl
authors.forename: Arjan
authors.initials: A
authors.lastname: van de Loosdrecht
keywords: PRAME; T- cell priming; WT1; acute myeloid leukemia; dendritic cell-based vaccination; immunotherapy