ArticleGene therapy2012
siRNA-mediated silencing of PD-1 ligands enhances tumor-specific human T-cell effector functions.
Article in Gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 60 citations in OpenAlex.
- Photothermal Therapeutic Gold Nanoparticles Loaded with PD-L1 siRNA Enhanced Killing of NSCLC Cells by Immune Cells.International journal of nanomedicine · 2025Article
- Molecular Engineering of Functional SiRNA Agents.ACS synthetic biology · 2024Article
- CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy.International journal of molecular sciences · 2023Article
- RNA Therapeutics for Improving CAR T-cell Safety and Efficacy.Cancer research · 2023Review
- Combination of genetically engineered T cells and immune checkpoint blockade for the treatment of cancer.Immunotherapy advances · 2022Review
- Application of lipid-based nanoparticles in cancer immunotherapy.Frontiers in immunology · 2022Review
- Tim-3 Blockade Elicits Potent Anti-Multiple Myeloma Immunity of Natural Killer Cells.Frontiers in oncology · 2022Article
- Use of dual-transfection for programmed death cell protein 1 disruption mediated by CRISPR-Cas9 in human peripheral blood mononuclear cells.Iranian journal of basic medical sciences · 2021Article
- Cellular Uptake of siRNA-Loaded Nanocarriers to Knockdown PD-L1: Strategies to Improve T-cell Functions.Cells · 2020Article
- Editing of Endogenous Genes in Cellular Immunotherapies.Current hematologic malignancy reports · 2020Review
- Tumor Immune Microenvironments (TIMEs): Responsive Nanoplatforms for Antitumor Immunotherapy.Frontiers in chemistry · 2020Review
- Silica Nanocapsules with Different Sizes and Physicochemical Properties as Suitable Nanocarriers for Uptake in T-Cells.International journal of nanomedicine · 2020Article
- The Role of Breast Cancer Stem Cells as a Prognostic Marker and a Target to Improve the Efficacy of Breast Cancer Therapy.Cancers · 2019Review
- Biodegradable Polymeric Nanoparticles for Therapeutic Cancer Treatments.Annual review of chemical and biomolecular engineering · 2018Review
- Cancer Immunotherapy: A Focus on the Regulation of Immune Checkpoints.International journal of molecular sciences · 2018Review
- CRISPR knock out of programmed cell death protein 1 enhances anti-tumor activity of cytotoxic T lymphocytes.Oncotarget · 2018Article
- Efficient and Non-genotoxic RNA-Based Engineering of Human T Cells Using Tumor-Specific T Cell Receptors With Minimal TCR Mispairing.Frontiers in immunology · 2018Article
- Cancer immunotherapy using PolyPurine Reverse Hoogsteen hairpins targeting the PD-1/PD-L1 pathway in human tumor cells.PloS one · 2018Article
- Nanomaterials for cancer immunotherapy.Biomaterials · 2017Review
- CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adoptive cell therapy using tumor-specific T cells is a promising strategy for treating patients with malignancy. However, accumulating evidences have demonstrated that optimal function of tumor-reactive T cells is often attenuated by negative regulatory signal(s) delivered through receptors, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and their cognate ligands. Although systemic blocking of these molecules needs careful attention on the risk of uncontrolled immune activation, selective inhibition of negative signals in tumor-specific T cells by their genetic modification is an attractive approach to overcome immunological suppression in cancer patients. Here, we demonstrate the improved effector functions of tumor-specific CD4(+) and CD8(+) human T cells by small interfering RNA (siRNA) -mediated silencing of PD-1 ligands, PD-L1 or PD-L2. Tumor antigen MAGE-A4-specific human T-cell clones upregulated the expression of PD-1 ligands upon activation. siRNA-mediated knockdown of PD-L1 or -L2 enhanced the interferon-γ production and antigen-specific cytotoxicity of these cells. Peripheral blood mononuclear cells transduced with a retroviral vector encoding MAGE-A4-specific T-cell receptor α/β chains also increased their effector functions by this modification. These results suggest that siRNA-mediated knockdown of PD-1 ligands is an attractive strategy to inhibit a negative regulatory mechanism of tumor-specific T cells resulting in enhanced efficacy of adoptive T-cell therapy of cancer using genetically modified autologous lymphocytes.
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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.