ArticleThe Journal of experimental medicine2020
A Fas-4-1BB fusion protein converts a death to a pro-survival signal and enhances T cell therapy.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 58 citations in OpenAlex.
- Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma.Science translational medicine · 2026Trial
- Minor histocompatibility antigen TCR-T.Blood advances · 2026Review
- Engineering CAR-Vδ2 T cells to boost persistence and anti-tumor function.bioRxiv : the preprint server for biology · 2026Article
- A CD8αβ co-receptor modified to contain an intracellular CD28 signaling tail enhances TCR-engineered T cell function independent of solid-tumor-associated co-stimulatory ligands.Nature communications · 2026Article
- Fusion protein-mediated costimulation in engineered T cells: from intrinsic signaling to tumor microenvironment rewiring.Frontiers in immunology · 2026Review
- CAR-engineered lymphocyte persistence is governed by a FAS ligand-FAS autoregulatory circuit.Nature cancer · 2025Article
- A TGF-βR/IL-2R immunomodulatory fusion protein transforms immunosuppression into T cell activation to enhance adoptive T cell therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanisms of Resistance to CAR T-Cells and How to Overcome Them.Methods and protocols · 2025Review
- Targeted theranostic nanomedicine using targeted CT-imageable particles that release tebentafusp.Japanese journal of radiology · 2025Article
- Current developments in T-cell receptor therapy for acute myeloid leukemia.Blood advances · 2025Review
- Ablation of FAS confers allogeneic CD3Nature biomedical engineering · 2024Article
- T Cell Resistance: On the Mechanisms of T Cell Non-activation.Immune network · 2024Review
- Leucine zipper-based immunomagnetic purification of CAR T cells displaying multiple receptors.Nature biomedical engineering · 2024Article
- Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.Seminars in immunopathology · 2024Review
- Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities.Science translational medicine · 2024Article
- Comparative analysis of Bcl-2 family protein overexpression in CAR T cells alone and in combination with BH3 mimetics.Science translational medicine · 2024Article
- Tsyn-Seq: a T-cell Synapse-Based Antigen Identification Platform.Cancer immunology research · 2024Article
- Dual targeting of cancer metabolome and stress antigens affects transcriptomic heterogeneity and efficacy of engineered T cells.Nature immunology · 2024Article
- Strategies and rules for tuning TCR-derived therapy.Expert reviews in molecular medicine · 2023Review
- T cell receptor therapeutics: immunological targeting of the intracellular cancer proteome.Nature reviews. Drug discovery · 2023Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Adoptive T cell therapy (ACT) with genetically modified T cells has shown impressive results against some hematologic cancers, but efficacy in solid tumors can be limited by restrictive tumor microenvironments (TMEs). For example, Fas ligand is commonly overexpressed in TMEs and induces apoptosis in tumor-infiltrating, Fas receptor-positive lymphocytes. We engineered immunomodulatory fusion proteins (IFPs) to enhance ACT efficacy, combining an inhibitory receptor ectodomain with a costimulatory endodomain to convert negative into positive signals. We developed a Fas-4-1BB IFP that replaces the Fas intracellular tail with costimulatory 4-1BB. Fas-4-1BB IFP-engineered murine T cells exhibited increased pro-survival signaling, proliferation, antitumor function, and altered metabolism in vitro. In vivo, Fas-4-1BB ACT eradicated leukemia and significantly improved survival in the aggressive KPC pancreatic cancer model. Fas-4-1BB IFP expression also enhanced primary human T cell function in vitro. Thus, Fas-4-1BB IFP expression is a novel strategy to improve multiple T cell functions and enhance ACT against solid tumors and hematologic 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.