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Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products

Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phen...

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Autores principales: Nowicki, Theodore S., Escuin-Ordinas, Helena, Avramis, Earl, Chmielowski, Bartosz, Chodon, Thinle, Berent-Maoz, Beata, Wang, Xiaoyan, Kaplan-Lefko, Paula, Yang, Lili, Baltimore, David, Economou, James S., Ribas, Antoni, Comin-Anduix, Begoña
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959255/
https://www.ncbi.nlm.nih.gov/pubmed/29470191
http://dx.doi.org/10.1097/CJI.0000000000000216
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author Nowicki, Theodore S.
Escuin-Ordinas, Helena
Avramis, Earl
Chmielowski, Bartosz
Chodon, Thinle
Berent-Maoz, Beata
Wang, Xiaoyan
Kaplan-Lefko, Paula
Yang, Lili
Baltimore, David
Economou, James S.
Ribas, Antoni
Comin-Anduix, Begoña
author_facet Nowicki, Theodore S.
Escuin-Ordinas, Helena
Avramis, Earl
Chmielowski, Bartosz
Chodon, Thinle
Berent-Maoz, Beata
Wang, Xiaoyan
Kaplan-Lefko, Paula
Yang, Lili
Baltimore, David
Economou, James S.
Ribas, Antoni
Comin-Anduix, Begoña
author_sort Nowicki, Theodore S.
collection PubMed
description Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were divided into cohorts based on several manufacturing changes in the generation and administration of the transgenic T cells: decreasing ex vivo stimulation/expansion time, increased cell dose, and receiving fresh instead of cryopreserved cells. T-cell phenotypes were analyzed by flow cytometry at baseline and longitudinally in peripheral blood. Transgenic T cells with shorter ex vivo culture/expansion periods displayed significantly increased expression of markers associated with less differentiated naive/memory populations, as well as significantly decreased expression of the inhibitory receptor programmed death 1 (PD1). Patients receiving fresh infusions of transgenic cells demonstrated expansion of central memory T cells and delayed acquisition of PD1 expression compared with patients who received cryopreserved products. Freshly infused transgenic T cells showed persistence and expansion of naive and memory T-cell populations and delayed acquisition of PD1 expression, which correlated with this cohort’s superior persistence of transgenic cells and response to dendritic cell vaccines. These results may be useful in designing future ACT protocols.
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spelling pubmed-59592552018-06-01 Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products Nowicki, Theodore S. Escuin-Ordinas, Helena Avramis, Earl Chmielowski, Bartosz Chodon, Thinle Berent-Maoz, Beata Wang, Xiaoyan Kaplan-Lefko, Paula Yang, Lili Baltimore, David Economou, James S. Ribas, Antoni Comin-Anduix, Begoña J Immunother Clinical Studies Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were divided into cohorts based on several manufacturing changes in the generation and administration of the transgenic T cells: decreasing ex vivo stimulation/expansion time, increased cell dose, and receiving fresh instead of cryopreserved cells. T-cell phenotypes were analyzed by flow cytometry at baseline and longitudinally in peripheral blood. Transgenic T cells with shorter ex vivo culture/expansion periods displayed significantly increased expression of markers associated with less differentiated naive/memory populations, as well as significantly decreased expression of the inhibitory receptor programmed death 1 (PD1). Patients receiving fresh infusions of transgenic cells demonstrated expansion of central memory T cells and delayed acquisition of PD1 expression compared with patients who received cryopreserved products. Freshly infused transgenic T cells showed persistence and expansion of naive and memory T-cell populations and delayed acquisition of PD1 expression, which correlated with this cohort’s superior persistence of transgenic cells and response to dendritic cell vaccines. These results may be useful in designing future ACT protocols. Lippincott Williams & Wilkins 2018-06 2018-02-21 /pmc/articles/PMC5959255/ /pubmed/29470191 http://dx.doi.org/10.1097/CJI.0000000000000216 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Clinical Studies
Nowicki, Theodore S.
Escuin-Ordinas, Helena
Avramis, Earl
Chmielowski, Bartosz
Chodon, Thinle
Berent-Maoz, Beata
Wang, Xiaoyan
Kaplan-Lefko, Paula
Yang, Lili
Baltimore, David
Economou, James S.
Ribas, Antoni
Comin-Anduix, Begoña
Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products
title Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products
title_full Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products
title_fullStr Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products
title_full_unstemmed Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products
title_short Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products
title_sort characterization of postinfusion phenotypic differences in fresh versus cryopreserved tcr engineered adoptive cell therapy products
topic Clinical Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959255/
https://www.ncbi.nlm.nih.gov/pubmed/29470191
http://dx.doi.org/10.1097/CJI.0000000000000216
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