The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via Glycoengineering

Despite decades of intensive attention directed to creation of genetically altered cells (e.g., as in development of chimeric antigen receptor (CAR) T-cells) and/or to achieve requisite in vitro accumulation of desired immunologic effectors (e.g., elaboration of virus-specific T cells, expansion of...

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Main Author: Robert Sackstein
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.03084/full
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author Robert Sackstein
author_facet Robert Sackstein
author_sort Robert Sackstein
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description Despite decades of intensive attention directed to creation of genetically altered cells (e.g., as in development of chimeric antigen receptor (CAR) T-cells) and/or to achieve requisite in vitro accumulation of desired immunologic effectors (e.g., elaboration of virus-specific T cells, expansion of NK cells, differentiation of dendritic cells, isolation, and propagation of Tregs, etc.), there has been essentially no interest in the most fundamental of all hurdles: assuring tissue-specific delivery of administered therapeutic cells to sites where they are needed. With regards to use of CAR T-cells, the absence of information on the efficacy of cell delivery is striking, especially in light of the clear association between administered cell dose and adverse events, and the obvious fact that pertinent cell acquisition/expansion costs would be dramatically curtailed with more efficient delivery of the administered cell bolus. Herein, based on information garnered from studies of human leukocytes and adult stem cells, the logic underlying the use of cell surface glycoengineering to enforce E-selectin ligand expression will be conveyed in the context of how this approach offers strategies to enhance delivery of CAR T-cells to marrow and to tumor beds. This application of glycoscience principles and techniques with intention to optimize cell therapeutics is a prime example of the emerging field of “translational glycobiology.”
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spelling doaj.art-bc5dcdc70ec64213ba77139ff521d3942022-12-22T02:05:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-01-01910.3389/fimmu.2018.03084432295The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via GlycoengineeringRobert SacksteinDespite decades of intensive attention directed to creation of genetically altered cells (e.g., as in development of chimeric antigen receptor (CAR) T-cells) and/or to achieve requisite in vitro accumulation of desired immunologic effectors (e.g., elaboration of virus-specific T cells, expansion of NK cells, differentiation of dendritic cells, isolation, and propagation of Tregs, etc.), there has been essentially no interest in the most fundamental of all hurdles: assuring tissue-specific delivery of administered therapeutic cells to sites where they are needed. With regards to use of CAR T-cells, the absence of information on the efficacy of cell delivery is striking, especially in light of the clear association between administered cell dose and adverse events, and the obvious fact that pertinent cell acquisition/expansion costs would be dramatically curtailed with more efficient delivery of the administered cell bolus. Herein, based on information garnered from studies of human leukocytes and adult stem cells, the logic underlying the use of cell surface glycoengineering to enforce E-selectin ligand expression will be conveyed in the context of how this approach offers strategies to enhance delivery of CAR T-cells to marrow and to tumor beds. This application of glycoscience principles and techniques with intention to optimize cell therapeutics is a prime example of the emerging field of “translational glycobiology.”https://www.frontiersin.org/article/10.3389/fimmu.2018.03084/fullE-selectin ligandadoptive cell therapyCAR T cellGPSsialyl Lewis XsLeX
spellingShingle Robert Sackstein
The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via Glycoengineering
Frontiers in Immunology
E-selectin ligand
adoptive cell therapy
CAR T cell
GPS
sialyl Lewis X
sLeX
title The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via Glycoengineering
title_full The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via Glycoengineering
title_fullStr The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via Glycoengineering
title_full_unstemmed The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via Glycoengineering
title_short The First Step in Adoptive Cell Immunotherapeutics: Assuring Cell Delivery via Glycoengineering
title_sort first step in adoptive cell immunotherapeutics assuring cell delivery via glycoengineering
topic E-selectin ligand
adoptive cell therapy
CAR T cell
GPS
sialyl Lewis X
sLeX
url https://www.frontiersin.org/article/10.3389/fimmu.2018.03084/full
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