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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...

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Autores principales: Knochelmann, Hannah M., Smith, Aubrey S., Dwyer, Connor J., Wyatt, Megan M., Mehrotra, Shikhar, Paulos, Chrystal M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
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.
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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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