ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Targeting PD-L1 in cholangiocarcinoma using nanovesicle-based immunotherapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Engineered Natural Killer Cell Derived-Extracellular Vesicles: An Acellular Immunotherapy with Cytotoxic Effects in SNU-1079 Human Cholangiocarcinoma Cells.Molecular pharmaceutics · 2026Article
- CAR-T cells directed toward PD-L1 demonstrate potent, antigen-specific activity against cholangiocarcinoma: A proof of concept study.Molecular therapy. Oncology · 2026Article
- EpCAM-targeted ZIF-8 nanocarriers for enhanced doxorubicin delivery in cancer therapy: a promising approach for tumor-specific drug release.Scientific reports · 2026Article
- Amino acid metabolic reprogramming: future prospects for cholangiocarcinoma therapy.Cell death discovery · 2026Review
- Harnessing cellular immunotherapy for cholangiocarcinoma: an integrated roadmap for overcoming resistance.Frontiers in immunology · 2026Review
- Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy.Current issues in molecular biology · 2025Review
- Using aptamers for targeted delivery of RNA therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Metabolic collusion driving immune evasion in cholangiocarcinoma: unmasking the dual control of the immuno-metabolic microenvironment.Frontiers in immunology · 2025Review
- Advancing biliary tract malignancy treatment: emerging frontiers in cell-based therapies.Frontiers in immunology · 2025Review
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Mechanisms of biliary stricture and novel therapeutic strategies.Frontiers in medicine · 2025Review
- In Silico Design of Novel EpCAM-Binding Aptamers for Targeted Delivery of RNA Therapeutics.Nanomaterials (Basel, Switzerland) · 2024Article
- RNA therapeutics targeting PD-L1 is a promising immune-activation strategy against difficult-to-treat cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Organoids and spheroids: advancedFrontiers in cell and developmental biology · 2024Review
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6 authors.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.