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Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds

The long-standing promise for the application of engineered T lymphocytes to target and eradicate malignancy has begun to be realized recently, with remarkable clinical success reported by a number of groups using Chimeric Antigen Receptor –engineered T cells to target CD19-positive hematologic mali...

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Autor principal: Kalos, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754893/
https://www.ncbi.nlm.nih.gov/pubmed/26885367
http://dx.doi.org/10.1186/s40425-016-0108-2
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author Kalos, Michael
author_facet Kalos, Michael
author_sort Kalos, Michael
collection PubMed
description The long-standing promise for the application of engineered T lymphocytes to target and eradicate malignancy has begun to be realized recently, with remarkable clinical success reported by a number of groups using Chimeric Antigen Receptor –engineered T cells to target CD19-positive hematologic malignancies. In the September 2 issue of Science Translational Medicine, Porter et al. present the clinical data and correlative analyses for 14 CLL patients treated at the University of Pennsylvania under the pilot clinical trial recently completed at that institution. The initial reports from this trial, published in 2011 documented robust clinical activity in a small cohort of treated patients accompanied by logarithmic expansion, contraction, and long-term functional persistence of engineered T cells, along with cytokine release syndrome as a side-effect of the treatment. In this latest report, updated data are presented from the initial cohort of patients, as well as clinical and correlative data from the remainder of the treated cohort. The robust clinical activity observed in the initial cohort continued to be observed in a subset of the subsequently-treated patients, with molecular remissions documented in that subset; however, in the expanded cohort a subset of partial and non-responding patients was also identified. Collectively, the results from this exciting trial provide evidence to suggest that cellular immunotherapy using engineered T cells is a viable option for treating CLL, reveal a likely requirement for robust in-vivo activation and persistence of engineered cells to effect complete responses, and also highlight the need for a more complete mechanistic understanding of the immune- and tumor- specific processes that define and dictate the success of this powerful treatment modality.
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spelling pubmed-47548932016-02-17 Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds Kalos, Michael J Immunother Cancer Commentary The long-standing promise for the application of engineered T lymphocytes to target and eradicate malignancy has begun to be realized recently, with remarkable clinical success reported by a number of groups using Chimeric Antigen Receptor –engineered T cells to target CD19-positive hematologic malignancies. In the September 2 issue of Science Translational Medicine, Porter et al. present the clinical data and correlative analyses for 14 CLL patients treated at the University of Pennsylvania under the pilot clinical trial recently completed at that institution. The initial reports from this trial, published in 2011 documented robust clinical activity in a small cohort of treated patients accompanied by logarithmic expansion, contraction, and long-term functional persistence of engineered T cells, along with cytokine release syndrome as a side-effect of the treatment. In this latest report, updated data are presented from the initial cohort of patients, as well as clinical and correlative data from the remainder of the treated cohort. The robust clinical activity observed in the initial cohort continued to be observed in a subset of the subsequently-treated patients, with molecular remissions documented in that subset; however, in the expanded cohort a subset of partial and non-responding patients was also identified. Collectively, the results from this exciting trial provide evidence to suggest that cellular immunotherapy using engineered T cells is a viable option for treating CLL, reveal a likely requirement for robust in-vivo activation and persistence of engineered cells to effect complete responses, and also highlight the need for a more complete mechanistic understanding of the immune- and tumor- specific processes that define and dictate the success of this powerful treatment modality. BioMed Central 2016-02-16 /pmc/articles/PMC4754893/ /pubmed/26885367 http://dx.doi.org/10.1186/s40425-016-0108-2 Text en © Kalos. 2016 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 Commentary
Kalos, Michael
Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds
title Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds
title_full Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds
title_fullStr Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds
title_full_unstemmed Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds
title_short Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds
title_sort chimeric antigen receptor-engineered t cells in cll: the next chapter unfolds
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754893/
https://www.ncbi.nlm.nih.gov/pubmed/26885367
http://dx.doi.org/10.1186/s40425-016-0108-2
work_keys_str_mv AT kalosmichael chimericantigenreceptorengineeredtcellsincllthenextchapterunfolds