دورية أكاديمية
Targeting PD-L1 in cholangiocarcinoma using nanovesicle-based immunotherapy.
| العنوان: | Targeting PD-L1 in cholangiocarcinoma using nanovesicle-based immunotherapy. |
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| المؤلفون: | Gondaliya P; Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA., Sayyed AA; Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA., Yan IK; Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA., Driscoll J; Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA., Ziemer A; Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA., Patel T; Departments of Transplantation and Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: patel.tushar@mayo.edu. |
| المصدر: | Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2024 Aug 07; Vol. 32 (8), pp. 2762-2777. Date of Electronic Publication: 2024 Jun 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 100890581 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-0024 (Electronic) Linking ISSN: 15250016 NLM ISO Abbreviation: Mol Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : Cambridge, MA : Cell Press Original Publication: San Diego, CA : Academic Press, 2000- |
| مواضيع طبية MeSH: | Cholangiocarcinoma*/therapy , Cholangiocarcinoma*/metabolism , Cholangiocarcinoma*/immunology , Cholangiocarcinoma*/drug therapy , Cholangiocarcinoma*/pathology , B7-H1 Antigen*/metabolism , B7-H1 Antigen*/antagonists & inhibitors , B7-H1 Antigen*/genetics , Immunotherapy*/methods , RNA, Small Interfering*/genetics , RNA, Small Interfering*/administration & dosage, Animals ; Humans ; Mice ; Cell Line, Tumor ; Nanoparticles/chemistry ; Bile Duct Neoplasms/therapy ; Bile Duct Neoplasms/pathology ; Bile Duct Neoplasms/metabolism ; Bile Duct Neoplasms/immunology ; Tumor Microenvironment/immunology ; Disease Models, Animal ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Gemcitabine |
| مستخلص: | This study demonstrates the potential of using biological nanoparticles to deliver RNA therapeutics targeting programmed death-ligand 1 (PD-L1) as a treatment strategy for cholangiocarcinoma (CCA). RNA therapeutics offer prospects for intracellular immune modulation, but effective clinical translation requires appropriate delivery strategies. Milk-derived nanovesicles were decorated with epithelial cellular adhesion molecule (EpCAM) aptamers and used to deliver PD-L1 small interfering RNA (siRNA) or Cas9 ribonucleoproteins directly to CCA cells. In vitro, nanovesicle treatments reduced PD-L1 expression in CCA cells while increasing degranulation, cytokine release, and tumor cell cytotoxicity when tumor cells were co-cultured with T cells or natural killer cells. Similarly, immunomodulation was observed in multicellular spheroids that mimicked the tumor microenvironment. Combining targeted therapeutic vesicles loaded with siRNA to PD-L1 with gemcitabine effectively reduced tumor burden in an immunocompetent mouse CCA model compared with controls. This proof-of-concept study demonstrates the potential of engineered targeted nanovesicle platforms for delivering therapeutic RNA cargoes to tumors, as well as their use in generating effective targeted immunomodulatory therapies for difficult-to-treat cancers such as CCA. Competing Interests: Declaration of interests The authors declare no conflict of interest. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: RNA therapeutics; biological nanoparticles; gene silencing; immunotherapy; milk-derived nanovesicles; targeted delivery |
| المشرفين على المادة: | 0 (B7-H1 Antigen) 0 (RNA, Small Interfering) 0 (CD274 protein, human) 0W860991D6 (Deoxycytidine) 0 (Gemcitabine) |
| تواريخ الأحداث: | Date Created: 20240611 Date Completed: 20240808 Latest Revision: 20240809 |
| رمز التحديث: | 20240812 |
| DOI: | 10.1016/j.ymthe.2024.06.006 |
| PMID: | 38859589 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1525-0024 |
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| DOI: | 10.1016/j.ymthe.2024.06.006 |