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Adoptive cell therapy using PD-1(+) myeloma-reactive T cells eliminates established myeloma in mice

BACKGROUND: Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication re...

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Autores principales: Jing, Weiqing, Gershan, Jill A., Blitzer, Grace C., Palen, Katie, Weber, James, McOlash, Laura, Riese, Matthew, Johnson, Bryon D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477110/
https://www.ncbi.nlm.nih.gov/pubmed/28642819
http://dx.doi.org/10.1186/s40425-017-0256-z
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author Jing, Weiqing
Gershan, Jill A.
Blitzer, Grace C.
Palen, Katie
Weber, James
McOlash, Laura
Riese, Matthew
Johnson, Bryon D.
author_facet Jing, Weiqing
Gershan, Jill A.
Blitzer, Grace C.
Palen, Katie
Weber, James
McOlash, Laura
Riese, Matthew
Johnson, Bryon D.
author_sort Jing, Weiqing
collection PubMed
description BACKGROUND: Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers. METHODS: PD-1(+) and PD-1(−) T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro. In addition, the T cells were activated and expanded in culture and given to syngeneic myeloma-bearing mice as ACT. RESULTS: Myeloma-reactive T cells were enriched in the PD-1(+) cell subset. Similar results were also observed in a mouse AML model. PD-1(+) T cells from myeloma-bearing mice were found to be functional, they could be activated and expanded ex vivo, and they maintained their anti-myeloma reactivity after expansion. Adoptive transfer of ex vivo-expanded PD-1(+) T cells together with a PD-L1 blocking antibody eliminated established myeloma in Rag-deficient mice. Both CD8 and CD4 T cell subsets were important for eradicating myeloma. Adoptively transferred PD-1(+) T cells persisted in recipient mice and were able to mount an adaptive memory immune response. CONCLUSIONS: These results demonstrate that PD-1 is a biomarker for functional myeloma-specific T cells, and that activated and expanded PD-1(+) T cells can be effective as ACT for myeloma. Furthermore, this strategy could be useful for treating other hematologic cancers.
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spelling pubmed-54771102017-06-22 Adoptive cell therapy using PD-1(+) myeloma-reactive T cells eliminates established myeloma in mice Jing, Weiqing Gershan, Jill A. Blitzer, Grace C. Palen, Katie Weber, James McOlash, Laura Riese, Matthew Johnson, Bryon D. J Immunother Cancer Research Article BACKGROUND: Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers. METHODS: PD-1(+) and PD-1(−) T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro. In addition, the T cells were activated and expanded in culture and given to syngeneic myeloma-bearing mice as ACT. RESULTS: Myeloma-reactive T cells were enriched in the PD-1(+) cell subset. Similar results were also observed in a mouse AML model. PD-1(+) T cells from myeloma-bearing mice were found to be functional, they could be activated and expanded ex vivo, and they maintained their anti-myeloma reactivity after expansion. Adoptive transfer of ex vivo-expanded PD-1(+) T cells together with a PD-L1 blocking antibody eliminated established myeloma in Rag-deficient mice. Both CD8 and CD4 T cell subsets were important for eradicating myeloma. Adoptively transferred PD-1(+) T cells persisted in recipient mice and were able to mount an adaptive memory immune response. CONCLUSIONS: These results demonstrate that PD-1 is a biomarker for functional myeloma-specific T cells, and that activated and expanded PD-1(+) T cells can be effective as ACT for myeloma. Furthermore, this strategy could be useful for treating other hematologic cancers. BioMed Central 2017-06-20 /pmc/articles/PMC5477110/ /pubmed/28642819 http://dx.doi.org/10.1186/s40425-017-0256-z Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Jing, Weiqing
Gershan, Jill A.
Blitzer, Grace C.
Palen, Katie
Weber, James
McOlash, Laura
Riese, Matthew
Johnson, Bryon D.
Adoptive cell therapy using PD-1(+) myeloma-reactive T cells eliminates established myeloma in mice
title Adoptive cell therapy using PD-1(+) myeloma-reactive T cells eliminates established myeloma in mice
title_full Adoptive cell therapy using PD-1(+) myeloma-reactive T cells eliminates established myeloma in mice
title_fullStr Adoptive cell therapy using PD-1(+) myeloma-reactive T cells eliminates established myeloma in mice
title_full_unstemmed Adoptive cell therapy using PD-1(+) myeloma-reactive T cells eliminates established myeloma in mice
title_short Adoptive cell therapy using PD-1(+) myeloma-reactive T cells eliminates established myeloma in mice
title_sort adoptive cell therapy using pd-1(+) myeloma-reactive t cells eliminates established myeloma in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477110/
https://www.ncbi.nlm.nih.gov/pubmed/28642819
http://dx.doi.org/10.1186/s40425-017-0256-z
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