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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2018
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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. |
format | Online Article Text |
id | pubmed-5959255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
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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