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Allogeneic CAR Cell Therapy—More Than a Pipe Dream

Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) has shown promise, particularly for the treatment of hematological malignancies. To date, the majority of clinically evaluated CAR cell products have been derived from autologous immune cells. While this...

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Autores principales: Caldwell, Kenneth J., Gottschalk, Stephen, Talleur, Aimee C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821739/
https://www.ncbi.nlm.nih.gov/pubmed/33488631
http://dx.doi.org/10.3389/fimmu.2020.618427
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author Caldwell, Kenneth J.
Gottschalk, Stephen
Talleur, Aimee C.
author_facet Caldwell, Kenneth J.
Gottschalk, Stephen
Talleur, Aimee C.
author_sort Caldwell, Kenneth J.
collection PubMed
description Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) has shown promise, particularly for the treatment of hematological malignancies. To date, the majority of clinically evaluated CAR cell products have been derived from autologous immune cells. While this strategy can be effective it also imposes several constraints regarding logistics. This includes i) availability of center to perform leukapheresis, ii) necessity for shipment to and from processing centers, and iii) time requirements for product manufacture and clinical release testing. In addition, previous cytotoxic therapies can negatively impact the effector function of autologous immune cells, which may then affect efficacy and/or durability of resultant CAR products. The use of allogeneic CAR cell products generated using cells from healthy donors has the potential to overcome many of these limitations, including through generation of “off the shelf” products. However, allogeneic CAR cell products come with their own challenges, including potential to induce graft-versus-host-disease, as well as risk of immune-mediated rejection by the host. Here we will review promises and challenges of allogeneic CAR immunotherapies, including those being investigated in preclinical models and/or early phase clinical studies.
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spelling pubmed-78217392021-01-23 Allogeneic CAR Cell Therapy—More Than a Pipe Dream Caldwell, Kenneth J. Gottschalk, Stephen Talleur, Aimee C. Front Immunol Immunology Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) has shown promise, particularly for the treatment of hematological malignancies. To date, the majority of clinically evaluated CAR cell products have been derived from autologous immune cells. While this strategy can be effective it also imposes several constraints regarding logistics. This includes i) availability of center to perform leukapheresis, ii) necessity for shipment to and from processing centers, and iii) time requirements for product manufacture and clinical release testing. In addition, previous cytotoxic therapies can negatively impact the effector function of autologous immune cells, which may then affect efficacy and/or durability of resultant CAR products. The use of allogeneic CAR cell products generated using cells from healthy donors has the potential to overcome many of these limitations, including through generation of “off the shelf” products. However, allogeneic CAR cell products come with their own challenges, including potential to induce graft-versus-host-disease, as well as risk of immune-mediated rejection by the host. Here we will review promises and challenges of allogeneic CAR immunotherapies, including those being investigated in preclinical models and/or early phase clinical studies. Frontiers Media S.A. 2021-01-08 /pmc/articles/PMC7821739/ /pubmed/33488631 http://dx.doi.org/10.3389/fimmu.2020.618427 Text en Copyright © 2021 Caldwell, Gottschalk and Talleur http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Caldwell, Kenneth J.
Gottschalk, Stephen
Talleur, Aimee C.
Allogeneic CAR Cell Therapy—More Than a Pipe Dream
title Allogeneic CAR Cell Therapy—More Than a Pipe Dream
title_full Allogeneic CAR Cell Therapy—More Than a Pipe Dream
title_fullStr Allogeneic CAR Cell Therapy—More Than a Pipe Dream
title_full_unstemmed Allogeneic CAR Cell Therapy—More Than a Pipe Dream
title_short Allogeneic CAR Cell Therapy—More Than a Pipe Dream
title_sort allogeneic car cell therapy—more than a pipe dream
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821739/
https://www.ncbi.nlm.nih.gov/pubmed/33488631
http://dx.doi.org/10.3389/fimmu.2020.618427
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