ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Clinical Scale Zinc Finger Nuclease-mediated Gene Editing of PD-1 in Tumor Infiltrating Lymphocytes for the Treatment of Metastatic Melanoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 111 citations in OpenAlex.
- Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer.Nature medicine · 2020Trial
- PD-1Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- From mechanism to medicine: CRISPR‒Cas9 delivery strategies, therapeutic applications and translation challenges.Discover nano · 2026Review
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- The opportunities and barriers for developing tumour-infiltrating lymphocyte therapy for patients with advanced genitourinary cancers.Nature reviews. Urology · 2026Review
- Peptide-MHC-targeted retroviruses enable in vivo expansion and gene delivery to tumor-specific T cells.Science advances · 2025Article
- CRISPR/Cas9-mediated PD-1 attenuation enhances tumor infiltrating lymphocyte-based adoptive cellular therapy in humanized-PDX model of hepatocellular carcinoma.Translational oncology · 2025Article
- Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.Molecular therapy. Nucleic acids · 2025Review
- Enhanced anti-tumor activity by zinc finger repressor-driven epigenetic silencing of immune checkpoints and TGFBR2 in CAR-T cells and TILs.Molecular therapy. Oncology · 2025Article
- Developing innovative strategies of tumor‑infiltrating lymphocyte therapy for tumor treatment.Oncology reports · 2024Review
- Advancements in clinical RNA therapeutics: Present developments and prospective outlooks.Cell reports. Medicine · 2024Review
- Enhanced cellular therapy: revolutionizing adoptive cellular therapy.Experimental hematology & oncology · 2024Review
- Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.Experimental hematology & oncology · 2024Review
- Tumour-infiltrating lymphocyte therapy for patients with advanced-stage melanoma.Nature reviews. Clinical oncology · 2024Review
- Engineering Challenges and Opportunities in Autologous Cellular Cancer Immunotherapy.Journal of immunology (Baltimore, Md. : 1950) · 2024Review
- Reversing T Cell Exhaustion by Converting Membrane PD-1 to Its Soluble form in Jurkat Cells; Applying The CRISPR/Cas9 Exon Skipping Strategy.Cell journal · 2023Article
- Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy.Translational vision science & technology · 2023Article
- Advancing cell-based cancer immunotherapy through stem cell engineering.Cell stem cell · 2023Review
- CRISPR/Cas9 therapeutics: progress and prospects.Signal transduction and targeted therapy · 2023Review
- Current strategies employed in the manipulation of gene expression for clinical purposes.Journal of translational medicine · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
Programmed cell death-1 (PD-1) is expressed on activated T cells and represents an attractive target for gene-editing of tumor targeted T cells prior to adoptive cell transfer (ACT). We used zinc finger nucleases (ZFNs) directed against the gene encoding human PD-1 (PDCD-1) to gene-edit melanoma tumor infiltrating lymphocytes (TIL). We show that our clinical scale TIL production process yielded efficient modification of the PD-1 gene locus, with an average modification frequency of 74.8% (n = 3, range 69.9-84.1%) of the alleles in a bulk TIL population, which resulted in a 76% reduction in PD-1 surface-expression. Forty to 48% of PD-1 gene-edited cells had biallelic PD-1 modification. Importantly, the PD-1 gene-edited TIL product showed improved in vitro effector function and a significantly increased polyfunctional cytokine profile (TNFα, GM-CSF, and IFNγ) compared to unmodified TIL in two of the three donors tested. In addition, all donor cells displayed an effector memory phenotype and expanded approximately 500-2,000-fold in vitro. Thus, further study to determine the efficiency and safety of adoptive cell transfer using PD-1 gene-edited TIL for the treatment of metastatic melanoma is warranted.
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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.