Unlocking the power of immunotherapy : Combinatorial delivery of plasmid IL-15 and gemcitabine to synergistically remodeling the tumor microenvironment
Copyright © 2024 Elsevier B.V. All rights reserved..
Cancer immunotherapy has emerged as a promising clinical treatment strategy in recent years. Unfortunately, the satisfactory antitumor therapeutic efficacy of immunotherapy is limited by intricate immunosuppressive tumor microenvironment (ITM). To remodel the ITM and alleviate the immune evasion, we constructed FA-PEG-modified liposomes to deliver plasmid IL-15 (pIL-15) and gemcitabine (GEM) (FPCLpIL-15 + FPGL), respectively. The FPCL@pIL-15 (150 nm) and FPGL (120 nm) exhibited symmetrically spherical structures as well as desirable penetration and accumulation on tumor tissue depending on folic acid (FA) specialized targeting function. The transfected expression of IL-15 efficiently fosters the proliferation and co-activation of Natural killer (NK) cells and CD8+T cells through binding to IL-15R. FPGL upregulated the expression of Natural killer group 2 member D ligands (NKG2DLs) and reinforced recognition by NK cells to alleviate the immune evasion, and simultaneously promoted activation of CD8+T cells through immunogenic cell death (ICD) effects. More importantly, the combinatorial administration achieved intended anti-tumor efficacy in the subcutaneous 4T1 tumor model. In essence, we demonstrated that combining FPCL@pIL-15 with FPGL synergistically stimulates and mobilizes the immune system to reverse the ITM and trigger an anti-tumor immune response, indicating a tremendous potential for application in immunotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:655 |
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| Enthalten in: |
International journal of pharmaceutics - 655(2024) vom: 25. Apr., Seite 124027 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Jingwen [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer immunotherapy |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 16.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpharm.2024.124027 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370442652 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Cancer immunotherapy has emerged as a promising clinical treatment strategy in recent years. Unfortunately, the satisfactory antitumor therapeutic efficacy of immunotherapy is limited by intricate immunosuppressive tumor microenvironment (ITM). To remodel the ITM and alleviate the immune evasion, we constructed FA-PEG-modified liposomes to deliver plasmid IL-15 (pIL-15) and gemcitabine (GEM) (FPCLpIL-15 + FPGL), respectively. The FPCL@pIL-15 (150 nm) and FPGL (120 nm) exhibited symmetrically spherical structures as well as desirable penetration and accumulation on tumor tissue depending on folic acid (FA) specialized targeting function. The transfected expression of IL-15 efficiently fosters the proliferation and co-activation of Natural killer (NK) cells and CD8+T cells through binding to IL-15R. FPGL upregulated the expression of Natural killer group 2 member D ligands (NKG2DLs) and reinforced recognition by NK cells to alleviate the immune evasion, and simultaneously promoted activation of CD8+T cells through immunogenic cell death (ICD) effects. More importantly, the combinatorial administration achieved intended anti-tumor efficacy in the subcutaneous 4T1 tumor model. In essence, we demonstrated that combining FPCL@pIL-15 with FPGL synergistically stimulates and mobilizes the immune system to reverse the ITM and trigger an anti-tumor immune response, indicating a tremendous potential for application in immunotherapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cancer immunotherapy | |
| 650 | 4 | |a Immunogenic cell death | |
| 650 | 4 | |a Immunosuppressive tumor microenvironment | |
| 650 | 4 | |a NKG2D-NKG2DLs axis | |
| 650 | 7 | |a Gemcitabine |2 NLM | |
| 650 | 7 | |a Interleukin-15 |2 NLM | |
| 700 | 1 | |a Han, Yanyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Leyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Haiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Dawei |e verfasserin |4 aut | |
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