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CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies
Genetic redirection of T lymphocytes with chimeric antigen receptors (CARs) has soared from treating cancers preclinically to FDA approval for hematologic malignancies and commercial-grade production scale in under 30 years. To date, solid tumors are less susceptible to CAR therapies and instead hav...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094980/ https://www.ncbi.nlm.nih.gov/pubmed/30140266 http://dx.doi.org/10.3389/fimmu.2018.01740 |
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author | Knochelmann, Hannah M. Smith, Aubrey S. Dwyer, Connor J. Wyatt, Megan M. Mehrotra, Shikhar Paulos, Chrystal M. |
author_facet | Knochelmann, Hannah M. Smith, Aubrey S. Dwyer, Connor J. Wyatt, Megan M. Mehrotra, Shikhar Paulos, Chrystal M. |
author_sort | Knochelmann, Hannah M. |
collection | PubMed |
description | Genetic redirection of T lymphocytes with chimeric antigen receptors (CARs) has soared from treating cancers preclinically to FDA approval for hematologic malignancies and commercial-grade production scale in under 30 years. To date, solid tumors are less susceptible to CAR therapies and instead have been treated more successfully with immune checkpoint blockade or tumor-infiltrating lymphocyte therapy. Here, we discuss the current challenges in treating solid tumors with CAR T cells, and the obstacles within the host and tumor microenvironment hindering their efficacy. We present a novel three-pronged approach for enhancing the efficacy of CAR T cells whereby a single infusion product can synergize the power of an optimal CAR construct, a highly potent T cell subset, and rejuvenate the endogenous immune response to conquer therapeutically-resistant solid tumors. |
format | Online Article Text |
id | pubmed-6094980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60949802018-08-23 CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies Knochelmann, Hannah M. Smith, Aubrey S. Dwyer, Connor J. Wyatt, Megan M. Mehrotra, Shikhar Paulos, Chrystal M. Front Immunol Immunology Genetic redirection of T lymphocytes with chimeric antigen receptors (CARs) has soared from treating cancers preclinically to FDA approval for hematologic malignancies and commercial-grade production scale in under 30 years. To date, solid tumors are less susceptible to CAR therapies and instead have been treated more successfully with immune checkpoint blockade or tumor-infiltrating lymphocyte therapy. Here, we discuss the current challenges in treating solid tumors with CAR T cells, and the obstacles within the host and tumor microenvironment hindering their efficacy. We present a novel three-pronged approach for enhancing the efficacy of CAR T cells whereby a single infusion product can synergize the power of an optimal CAR construct, a highly potent T cell subset, and rejuvenate the endogenous immune response to conquer therapeutically-resistant solid tumors. Frontiers Media S.A. 2018-07-27 /pmc/articles/PMC6094980/ /pubmed/30140266 http://dx.doi.org/10.3389/fimmu.2018.01740 Text en Copyright © 2018 Knochelmann, Smith, Dwyer, Wyatt, Mehrotra and Paulos. https://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 Knochelmann, Hannah M. Smith, Aubrey S. Dwyer, Connor J. Wyatt, Megan M. Mehrotra, Shikhar Paulos, Chrystal M. CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies |
title | CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies |
title_full | CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies |
title_fullStr | CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies |
title_full_unstemmed | CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies |
title_short | CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies |
title_sort | car t cells in solid tumors: blueprints for building effective therapies |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094980/ https://www.ncbi.nlm.nih.gov/pubmed/30140266 http://dx.doi.org/10.3389/fimmu.2018.01740 |
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