ArticleThe Journal of clinical investigation2019
T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
100 citing papers in PubMed, 153 citations in OpenAlex.
- Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.Signal transduction and targeted therapy · 2026Review
- Integrated epigenetic and genetic programming of primary human T cells.Nature biotechnology · 2026Article
- Adenine base editor for knockout of proteins: A practical guide from design to analysis with updated MultiEditRbatch.Molecular therapy. Nucleic acids · 2026Article
- Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Engineering CAR-Vδ2 T cells to boost persistence and anti-tumor function.bioRxiv : the preprint server for biology · 2026Article
- Co-editing of NKG2A and FAS increases long-term cytotoxic capacity and persistence of CAR NK cells.Molecular therapy. Oncology · 2026Article
- QBEmax is a sequence-permuted and internally protected base editor.Nature biotechnology · 2026Article
- A multidimensional workflow profiling of allogeneic virus-specific T cell therapies reveals potency-linked signatures.Nature communications · 2026Article
- Fusion protein-mediated costimulation in engineered T cells: from intrinsic signaling to tumor microenvironment rewiring.Frontiers in immunology · 2026Review
- Installation of dominant-negative mutations inMolecular therapy. Oncology · 2025Article
- Tumour-associated vasculature in T cell homing and immunity: opportunities for cancer therapy.Nature reviews. Immunology · 2025Review
- CAR-engineered lymphocyte persistence is governed by a FAS ligand-FAS autoregulatory circuit.Nature cancer · 2025Article
- Synthetic Biology and Biomaterials Strategies to Deceive the Tumor Microenvironment in CAR-T Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2025Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Installation of Dominant-Negative Mutations inbioRxiv : the preprint server for biology · 2025Article
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- Article
- Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012-2023).Human vaccines & immunotherapeutics · 2024Article
- Ablation of FAS confers allogeneic CD3Nature biomedical engineering · 2024Article
- CAR T cells in solid tumors and metastasis: paving the way forward.Cancer metastasis reviews · 2024Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 7 institutions in 1 country.
Funding
Abstract
Across clinical trials, T cell expansion and persistence following adoptive cell transfer (ACT) have correlated with superior patient outcomes. Herein, we undertook a pan-cancer analysis to identify actionable ligand-receptor pairs capable of compromising T cell durability following ACT. We discovered that FASLG, the gene encoding the apoptosis-inducing ligand FasL, is overexpressed within the majority of human tumor microenvironments (TMEs). Further, we uncovered that Fas, the receptor for FasL, is highly expressed on patient-derived T cells used for clinical ACT. We hypothesized that a cognate Fas-FasL interaction within the TME might limit both T cell persistence and antitumor efficacy. We discovered that genetic engineering of Fas variants impaired in the ability to bind FADD functioned as dominant negative receptors (DNRs), preventing FasL-induced apoptosis in Fas-competent T cells. T cells coengineered with a Fas DNR and either a T cell receptor or chimeric antigen receptor exhibited enhanced persistence following ACT, resulting in superior antitumor efficacy against established solid and hematologic cancers. Despite increased longevity, Fas DNR-engineered T cells did not undergo aberrant expansion or mediate autoimmunity. Thus, T cell-intrinsic disruption of Fas signaling through genetic engineering represents a potentially universal strategy to enhance ACT efficacy across a broad range of human malignancies.
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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.