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In Situ Vaccination Following Intratumoral Injection of IL2 and Poly-l-lysine/Iron Oxide/CpG Nanoparticles to a Radiated Tumor Site

[Image: see text] The in situ vaccine effect of radiation therapy (RT) has been shown to be limited in both preclinical and clinical settings, possibly due to the inadequacy of RT alone to stimulate in situ vaccination in immunologically “cold” tumor microenvironments (TMEs) and the mixed effects of...

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Autores principales: Zhang, Ying, Rahman, Md Mahfuzur, Clark, Paul A., Sriramaneni, Raghava N., Havighurst, Thomas, Kerr, Caroline P., Zhu, Min, Jones, Jamie, Wang, Xiuxiu, Kim, KyungMann, Gong, Shaoqin, Morris, Zachary S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278176/
https://www.ncbi.nlm.nih.gov/pubmed/37216491
http://dx.doi.org/10.1021/acsnano.3c00418
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author Zhang, Ying
Rahman, Md Mahfuzur
Clark, Paul A.
Sriramaneni, Raghava N.
Havighurst, Thomas
Kerr, Caroline P.
Zhu, Min
Jones, Jamie
Wang, Xiuxiu
Kim, KyungMann
Gong, Shaoqin
Morris, Zachary S.
author_facet Zhang, Ying
Rahman, Md Mahfuzur
Clark, Paul A.
Sriramaneni, Raghava N.
Havighurst, Thomas
Kerr, Caroline P.
Zhu, Min
Jones, Jamie
Wang, Xiuxiu
Kim, KyungMann
Gong, Shaoqin
Morris, Zachary S.
author_sort Zhang, Ying
collection PubMed
description [Image: see text] The in situ vaccine effect of radiation therapy (RT) has been shown to be limited in both preclinical and clinical settings, possibly due to the inadequacy of RT alone to stimulate in situ vaccination in immunologically “cold” tumor microenvironments (TMEs) and the mixed effects of RT in promoting tumor infiltration of both effector and suppressor immune cells. To address these limitations, we combined intratumoral injection of the radiated site with IL2 and a multifunctional nanoparticle (PIC). The local injection of these agents produced a cooperative effect that favorably immunomodulated the irradiated TME, enhancing the activation of tumor-infiltrating T cells and improving systemic anti-tumor T cell immunity. In syngeneic murine tumor models, the PIC+IL2+RT combination significantly improved the tumor response, surpassing the single or dual combinations of these treatments. Furthermore, this treatment led to the activation of tumor-specific immune memory and improved abscopal effects. Our findings suggest that this strategy can be used to augment the in situ vaccine effect of RT in clinical settings.
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spelling pubmed-102781762023-06-20 In Situ Vaccination Following Intratumoral Injection of IL2 and Poly-l-lysine/Iron Oxide/CpG Nanoparticles to a Radiated Tumor Site Zhang, Ying Rahman, Md Mahfuzur Clark, Paul A. Sriramaneni, Raghava N. Havighurst, Thomas Kerr, Caroline P. Zhu, Min Jones, Jamie Wang, Xiuxiu Kim, KyungMann Gong, Shaoqin Morris, Zachary S. ACS Nano [Image: see text] The in situ vaccine effect of radiation therapy (RT) has been shown to be limited in both preclinical and clinical settings, possibly due to the inadequacy of RT alone to stimulate in situ vaccination in immunologically “cold” tumor microenvironments (TMEs) and the mixed effects of RT in promoting tumor infiltration of both effector and suppressor immune cells. To address these limitations, we combined intratumoral injection of the radiated site with IL2 and a multifunctional nanoparticle (PIC). The local injection of these agents produced a cooperative effect that favorably immunomodulated the irradiated TME, enhancing the activation of tumor-infiltrating T cells and improving systemic anti-tumor T cell immunity. In syngeneic murine tumor models, the PIC+IL2+RT combination significantly improved the tumor response, surpassing the single or dual combinations of these treatments. Furthermore, this treatment led to the activation of tumor-specific immune memory and improved abscopal effects. Our findings suggest that this strategy can be used to augment the in situ vaccine effect of RT in clinical settings. American Chemical Society 2023-05-22 /pmc/articles/PMC10278176/ /pubmed/37216491 http://dx.doi.org/10.1021/acsnano.3c00418 Text en © 2023 American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Zhang, Ying
Rahman, Md Mahfuzur
Clark, Paul A.
Sriramaneni, Raghava N.
Havighurst, Thomas
Kerr, Caroline P.
Zhu, Min
Jones, Jamie
Wang, Xiuxiu
Kim, KyungMann
Gong, Shaoqin
Morris, Zachary S.
In Situ Vaccination Following Intratumoral Injection of IL2 and Poly-l-lysine/Iron Oxide/CpG Nanoparticles to a Radiated Tumor Site
title In Situ Vaccination Following Intratumoral Injection of IL2 and Poly-l-lysine/Iron Oxide/CpG Nanoparticles to a Radiated Tumor Site
title_full In Situ Vaccination Following Intratumoral Injection of IL2 and Poly-l-lysine/Iron Oxide/CpG Nanoparticles to a Radiated Tumor Site
title_fullStr In Situ Vaccination Following Intratumoral Injection of IL2 and Poly-l-lysine/Iron Oxide/CpG Nanoparticles to a Radiated Tumor Site
title_full_unstemmed In Situ Vaccination Following Intratumoral Injection of IL2 and Poly-l-lysine/Iron Oxide/CpG Nanoparticles to a Radiated Tumor Site
title_short In Situ Vaccination Following Intratumoral Injection of IL2 and Poly-l-lysine/Iron Oxide/CpG Nanoparticles to a Radiated Tumor Site
title_sort in situ vaccination following intratumoral injection of il2 and poly-l-lysine/iron oxide/cpg nanoparticles to a radiated tumor site
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278176/
https://www.ncbi.nlm.nih.gov/pubmed/37216491
http://dx.doi.org/10.1021/acsnano.3c00418
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