ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Self-Delivering RNAi Targeting PD-1 Improves Tumor-Specific T Cell Functionality for Adoptive Cell Therapy of Malignant Melanoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Targeting Immune Checkpoint Proteins in Cancer Therapy and the Potential of RNAi-Based Immunotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Optimized chemical structure extends silencing duration of therapeutic siRNAs in dividing cancer and immune cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting tumor immune evasion: the role of PD-L1 siRNA in advancing cancer immunotherapy.Medical oncology (Northwood, London, England) · 2025Review
- Targeting Exosomal PD-L1 as a New Frontier in Cancer Immunotherapy.Current issues in molecular biology · 2025Review
- INTASYL self-delivering RNAi decreases TIGIT expression, enhancing NK cell cytotoxicity: a potential application to increase the efficacy of NK adoptive cell therapy against cancer.Cancer immunology, immunotherapy : CII · 2024Article
- Self-delivering RNAi immunotherapeutic PH-762 silences PD-1 to generate local and abscopal antitumor efficacy.Frontiers in immunology · 2024Article
- Harnessing novel strategies and cell types to overcome immune tolerance during adoptive cell therapy in cancer.Journal for immunotherapy of cancer · 2023Review
- RNA Therapeutics for Improving CAR T-cell Safety and Efficacy.Cancer research · 2023Review
- Opportunities and obstacles for the melanoma immunotherapy using T cell and chimeric antigen receptor T (CAR-T) applications: a literature review.Molecular biology reports · 2022Review
- Charge-Conversion Strategies for Nucleic Acid Delivery.Advanced functional materials · 2021Article
- RNA-based therapies: A cog in the wheel of lung cancer defense.Molecular cancer · 2021Review
- A thiol-bound drug reservoir enhances APR-246-induced mutant p53 tumor cell death.EMBO molecular medicine · 2021Article
- PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles Downregulate PD-1 Expression by Macrophages and Inhibit Tumor Growth : PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles.AAPS PharmSciTech · 2021Article
- Review
- Importance of microRNAs in Skin Oncogenesis and Their Suitability as Agents and Targets for Topical Therapy.Skin pharmacology and physiology · 2020Review
- Silica Nanocapsules with Different Sizes and Physicochemical Properties as Suitable Nanocarriers for Uptake in T-Cells.International journal of nanomedicine · 2020Article
- LINC00459 sponging miR-218 to elevate DKK3 inhibits proliferation and invasion in melanoma.Scientific reports · 2019Article
- Review
- Editorial focus: understanding off-target effects as the key to successful RNAi therapy.Cellular & molecular biology letters · 2019Review
- Functional features defining the efficacy of cholesterol-conjugated, self-deliverable, chemically modified siRNAs.Nucleic acids research · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 5 countries.
Funding
Abstract
Adoptive cell therapy (ACT) is becoming a prominent alternative therapeutic treatment for cancer patients relapsing on traditional therapies. In parallel, antibodies targeting immune checkpoint molecules, such as cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and cell death protein 1 pathway (PD-1), are rapidly being approved for multiple cancer types, including as first line therapy for PD-L1-expressing non-small-cell lung cancer. The combination of ACT and checkpoint blockade could substantially boost the efficacy of ACT. In this study, we generated a novel self-delivering small interfering RNA (siRNA) (sdRNA) that knocked down PD-1 expression on healthy donor T cells as well as patient-derived tumor-infiltrating lymphocytes (TIL). We have developed an alternative chemical modification of RNA backbone for improved stability and increased efficacy. Our results show that T cells treated with sdRNA specific for PD-1 had increased interferon γ (IFN-γ) secreting capacity and that this modality of gene expression interference could be utilized in our rapid expansion protocol for production of TIL for therapy. TIL expanded in the presence of PD-1-specific sdRNA performed with increased functionality against autologous tumor as compared to control TIL. This method of introducing RNAi into T cells to modify the expression of proteins could easily be adopted into any ACT protocol and will lead to the exploration of new combination therapies.
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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.