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

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...

Full description

Bibliographic Details
Main Authors:	van den Ancker, Willemijn, Ruben, Jurjen M., Westers, Theresia M., Wulandari, Dewi, Bontkes, Hetty J., Hooijberg, Erik, Stam, Anita G.M., Santegoets, Saskia J.A.M., Ossenkoppele, Gert J., de Gruijl, Tanja, van de Loosdrecht, Arjan
Format:	Online
Language:	English
Published:	Landes Bioscience 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654602/

id	pubmed-3654602
recordtype	oai_dc
spelling	pubmed-36546022013-06-03 Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy van den Ancker, Willemijn Ruben, Jurjen M. Westers, Theresia M. Wulandari, Dewi Bontkes, Hetty J. Hooijberg, Erik Stam, Anita G.M. Santegoets, Saskia J.A.M. Ossenkoppele, Gert J. de Gruijl, Tanja van de Loosdrecht, Arjan Brief Report 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. Landes Bioscience 2013-04-01 2013-04-01 /pmc/articles/PMC3654602/ /pubmed/23734332 http://dx.doi.org/10.4161/onci.23971 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	van den Ancker, Willemijn Ruben, Jurjen M. Westers, Theresia M. Wulandari, Dewi Bontkes, Hetty J. Hooijberg, Erik Stam, Anita G.M. Santegoets, Saskia J.A.M. Ossenkoppele, Gert J. de Gruijl, Tanja van de Loosdrecht, Arjan
spellingShingle	van den Ancker, Willemijn Ruben, Jurjen M. Westers, Theresia M. Wulandari, Dewi Bontkes, Hetty J. Hooijberg, Erik Stam, Anita G.M. Santegoets, Saskia J.A.M. Ossenkoppele, Gert J. de Gruijl, Tanja van de Loosdrecht, Arjan Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy
author_facet	van den Ancker, Willemijn Ruben, Jurjen M. Westers, Theresia M. Wulandari, Dewi Bontkes, Hetty J. Hooijberg, Erik Stam, Anita G.M. Santegoets, Saskia J.A.M. Ossenkoppele, Gert J. de Gruijl, Tanja van de Loosdrecht, Arjan
author_sort	van den Ancker, Willemijn
title	Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy
title_short	Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy
title_full	Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy
title_fullStr	Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy
title_full_unstemmed	Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission: Implications for immunotherapy
title_sort	priming of prame- and wt1-specific cd8+ t cells in healthy donors but not in aml patients in complete remission: implications for immunotherapy
description	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.
publisher	Landes Bioscience
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654602/
_version_	1611977942826483712

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

Similar Items