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Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy

BACKGROUND: Interleukin‐1 alpha (IL‐1α) is a pro‐inflammatory cytokine that can activate immune effector cells and trigger anti‐tumor immune responses. However, dose‐limiting toxicities including cytokine storm and hypotension has limited its use in the clinic as a cancer therapy. We propose that po...

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Autores principales: Hasibuzzaman, M. M., He, Rui, Khan, Ishrat Nourin, Sabharwal, Rasna, Salem, Aliasger K., Simons‐Burnett, Andrean Llewela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189482/
https://www.ncbi.nlm.nih.gov/pubmed/37206237
http://dx.doi.org/10.1002/btm2.10465
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author Hasibuzzaman, M. M.
He, Rui
Khan, Ishrat Nourin
Sabharwal, Rasna
Salem, Aliasger K.
Simons‐Burnett, Andrean Llewela
author_facet Hasibuzzaman, M. M.
He, Rui
Khan, Ishrat Nourin
Sabharwal, Rasna
Salem, Aliasger K.
Simons‐Burnett, Andrean Llewela
author_sort Hasibuzzaman, M. M.
collection PubMed
description BACKGROUND: Interleukin‐1 alpha (IL‐1α) is a pro‐inflammatory cytokine that can activate immune effector cells and trigger anti‐tumor immune responses. However, dose‐limiting toxicities including cytokine storm and hypotension has limited its use in the clinic as a cancer therapy. We propose that polymeric microparticle (MP)‐based delivery of IL‐1α will suppress the acute pro‐inflammatory side effects by allowing for slow and controlled release of IL‐1α systemically, while simultaneously triggering an anti‐tumor immune response. METHODS: Polyanhydride copolymers composed of 1,6‐bis‐(p‐carboxyphenoxy)‐hexane:sebacic 20:80 (CPH:SA 20:80) was utilized to fabricate MPs. Recombinant IL‐1α (rIL‐1α) was encapsulated into CPH:SA 20:80 MPs (IL‐1α‐MPs) and the MPs were characterized by size, charge, loading efficiency, and in‐vitro release and activity of IL‐1α. IL‐1α‐MPs were injected intraperitonially into head and neck squamous cell carcinoma (HNSCC)‐bearing C57Bl/6 mice and monitored for changes in weight, tumor growth, circulating cytokines/chemokines, hepatic and kidney enzymes, blood pressure, heart rate, and tumor‐infiltrating immune cells. RESULTS: CPH:SA IL‐1α‐MPs demonstrated sustained release kinetics of IL‐1α (100% protein released over 8–10 days) accompanied by minimal weight loss and systemic inflammation compared to rIL‐1α‐treated mice. Blood pressure measured by radiotelemetry in conscious mice demonstrates that rIL‐1α‐induced hypotension was prevented in IL‐1α‐MP‐treated mice. Liver and kidney enzymes were within normal range for all control and cytokine‐treated mice. Both rIL‐1α and IL‐1α‐MP‐treated mice showed similar delays in tumor growth and similar increases in tumor‐infiltrating CD3+ T cells, macrophages, and dendritic cells. CONCLUSIONS: CPH:SA‐based IL‐1α‐MPs generated a slow and sustained systemic release of IL‐1α resulting in reduced weight loss, systemic inflammation, and hypotension accompanied by an adequate anti‐tumor immune response in HNSCC‐tumor bearing mice. Therefore, MPs based on CPH:SA formulations may be promising as delivery vehicles for IL‐1α to achieve safe, effective, and durable antitumor responses for HNSCC patients.
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spelling pubmed-101894822023-05-18 Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy Hasibuzzaman, M. M. He, Rui Khan, Ishrat Nourin Sabharwal, Rasna Salem, Aliasger K. Simons‐Burnett, Andrean Llewela Bioeng Transl Med Research Articles BACKGROUND: Interleukin‐1 alpha (IL‐1α) is a pro‐inflammatory cytokine that can activate immune effector cells and trigger anti‐tumor immune responses. However, dose‐limiting toxicities including cytokine storm and hypotension has limited its use in the clinic as a cancer therapy. We propose that polymeric microparticle (MP)‐based delivery of IL‐1α will suppress the acute pro‐inflammatory side effects by allowing for slow and controlled release of IL‐1α systemically, while simultaneously triggering an anti‐tumor immune response. METHODS: Polyanhydride copolymers composed of 1,6‐bis‐(p‐carboxyphenoxy)‐hexane:sebacic 20:80 (CPH:SA 20:80) was utilized to fabricate MPs. Recombinant IL‐1α (rIL‐1α) was encapsulated into CPH:SA 20:80 MPs (IL‐1α‐MPs) and the MPs were characterized by size, charge, loading efficiency, and in‐vitro release and activity of IL‐1α. IL‐1α‐MPs were injected intraperitonially into head and neck squamous cell carcinoma (HNSCC)‐bearing C57Bl/6 mice and monitored for changes in weight, tumor growth, circulating cytokines/chemokines, hepatic and kidney enzymes, blood pressure, heart rate, and tumor‐infiltrating immune cells. RESULTS: CPH:SA IL‐1α‐MPs demonstrated sustained release kinetics of IL‐1α (100% protein released over 8–10 days) accompanied by minimal weight loss and systemic inflammation compared to rIL‐1α‐treated mice. Blood pressure measured by radiotelemetry in conscious mice demonstrates that rIL‐1α‐induced hypotension was prevented in IL‐1α‐MP‐treated mice. Liver and kidney enzymes were within normal range for all control and cytokine‐treated mice. Both rIL‐1α and IL‐1α‐MP‐treated mice showed similar delays in tumor growth and similar increases in tumor‐infiltrating CD3+ T cells, macrophages, and dendritic cells. CONCLUSIONS: CPH:SA‐based IL‐1α‐MPs generated a slow and sustained systemic release of IL‐1α resulting in reduced weight loss, systemic inflammation, and hypotension accompanied by an adequate anti‐tumor immune response in HNSCC‐tumor bearing mice. Therefore, MPs based on CPH:SA formulations may be promising as delivery vehicles for IL‐1α to achieve safe, effective, and durable antitumor responses for HNSCC patients. John Wiley & Sons, Inc. 2022-12-07 /pmc/articles/PMC10189482/ /pubmed/37206237 http://dx.doi.org/10.1002/btm2.10465 Text en © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Hasibuzzaman, M. M.
He, Rui
Khan, Ishrat Nourin
Sabharwal, Rasna
Salem, Aliasger K.
Simons‐Burnett, Andrean Llewela
Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy
title Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy
title_full Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy
title_fullStr Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy
title_full_unstemmed Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy
title_short Characterization of CPH:SA microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy
title_sort characterization of cph:sa microparticle‐based delivery of interleukin‐1 alpha for cancer immunotherapy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189482/
https://www.ncbi.nlm.nih.gov/pubmed/37206237
http://dx.doi.org/10.1002/btm2.10465
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