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Exploiting Phagocytic Checkpoints in Nanomedicine: Applications in Imaging and Combination Therapies

Recent interest in cancer immunotherapy has largely been focused on the adaptive immune system, particularly adoptive T-cell therapy and immune checkpoint blockade (ICB). Despite improvements in overall survival and progression-free survival across multiple cancer types, neither cell-based therapies...

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Autores principales: Landry, Madeleine R., Walker, Joshua M., Sun, Conroy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966415/
https://www.ncbi.nlm.nih.gov/pubmed/33748077
http://dx.doi.org/10.3389/fchem.2021.642530
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author Landry, Madeleine R.
Walker, Joshua M.
Sun, Conroy
author_facet Landry, Madeleine R.
Walker, Joshua M.
Sun, Conroy
author_sort Landry, Madeleine R.
collection PubMed
description Recent interest in cancer immunotherapy has largely been focused on the adaptive immune system, particularly adoptive T-cell therapy and immune checkpoint blockade (ICB). Despite improvements in overall survival and progression-free survival across multiple cancer types, neither cell-based therapies nor ICB results in durable disease control in the majority of patients. A critical component of antitumor immunity is the mononuclear phagocyte system and its role in both innate and adaptive immunity. The phagocytic functions of these cells have been shown to be modulated through multiple pathways, including the CD47-SIRPα axis, which is manipulated by cancer cells for immune evasion. In addition to CD47, tumors express a variety of other “don’t eat me” signals, including beta-2-microglobulin and CD24, and “eat me” signals, including calreticulin and phosphatidylserine. Therapies targeting these signals can lead to increased phagocytosis of cancer cells; however, because “don’t eat me” signals are markers of “self” on normal cells, treatment can result in negative off-target effects, such as anemia and B-cell depletion. Recent preclinical research has demonstrated the potential of nanocarriers to synergize with prophagocytic therapies, address the off-target effects, improve pharmacokinetics, and codeliver chemotherapeutics. The high surface area-to-volume ratio of nanoparticles paired with preferential size for passive targeting allows for greater accumulation of therapeutic cargo. In addition, nanomaterials hold promise as molecular imaging agents for the detection of phagocytic markers. This mini review highlights the unique capabilities of nanotechnology to expand the application and efficacy of immunotherapy through recently discovered phagocytotic checkpoint therapies.
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spelling pubmed-79664152021-03-18 Exploiting Phagocytic Checkpoints in Nanomedicine: Applications in Imaging and Combination Therapies Landry, Madeleine R. Walker, Joshua M. Sun, Conroy Front Chem Chemistry Recent interest in cancer immunotherapy has largely been focused on the adaptive immune system, particularly adoptive T-cell therapy and immune checkpoint blockade (ICB). Despite improvements in overall survival and progression-free survival across multiple cancer types, neither cell-based therapies nor ICB results in durable disease control in the majority of patients. A critical component of antitumor immunity is the mononuclear phagocyte system and its role in both innate and adaptive immunity. The phagocytic functions of these cells have been shown to be modulated through multiple pathways, including the CD47-SIRPα axis, which is manipulated by cancer cells for immune evasion. In addition to CD47, tumors express a variety of other “don’t eat me” signals, including beta-2-microglobulin and CD24, and “eat me” signals, including calreticulin and phosphatidylserine. Therapies targeting these signals can lead to increased phagocytosis of cancer cells; however, because “don’t eat me” signals are markers of “self” on normal cells, treatment can result in negative off-target effects, such as anemia and B-cell depletion. Recent preclinical research has demonstrated the potential of nanocarriers to synergize with prophagocytic therapies, address the off-target effects, improve pharmacokinetics, and codeliver chemotherapeutics. The high surface area-to-volume ratio of nanoparticles paired with preferential size for passive targeting allows for greater accumulation of therapeutic cargo. In addition, nanomaterials hold promise as molecular imaging agents for the detection of phagocytic markers. This mini review highlights the unique capabilities of nanotechnology to expand the application and efficacy of immunotherapy through recently discovered phagocytotic checkpoint therapies. Frontiers Media S.A. 2021-03-03 /pmc/articles/PMC7966415/ /pubmed/33748077 http://dx.doi.org/10.3389/fchem.2021.642530 Text en Copyright © 2021 Landry, Walker and Sun. 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 Chemistry
Landry, Madeleine R.
Walker, Joshua M.
Sun, Conroy
Exploiting Phagocytic Checkpoints in Nanomedicine: Applications in Imaging and Combination Therapies
title Exploiting Phagocytic Checkpoints in Nanomedicine: Applications in Imaging and Combination Therapies
title_full Exploiting Phagocytic Checkpoints in Nanomedicine: Applications in Imaging and Combination Therapies
title_fullStr Exploiting Phagocytic Checkpoints in Nanomedicine: Applications in Imaging and Combination Therapies
title_full_unstemmed Exploiting Phagocytic Checkpoints in Nanomedicine: Applications in Imaging and Combination Therapies
title_short Exploiting Phagocytic Checkpoints in Nanomedicine: Applications in Imaging and Combination Therapies
title_sort exploiting phagocytic checkpoints in nanomedicine: applications in imaging and combination therapies
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966415/
https://www.ncbi.nlm.nih.gov/pubmed/33748077
http://dx.doi.org/10.3389/fchem.2021.642530
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