ArticleJCI insight2021
Cell-targeted PD-1 agonists that mimic PD-L1 are potent T cell inhibitors.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 71 citations in OpenAlex.
- Understanding the Therapeutic Potential of PD-1 Agonism in Inflammatory and Autoimmune Disorders.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Selective depletion of virus-specific CD8 T cells from the liver after PD-1 therapy with Fc-intact antibody during chronic infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Beta cell-targeted PD-1 agonist inhibits cell-mediated autoimmunity in pancreas tissue slices.Science advances · 2026Article
- From bench to bedside: stem cell therapy as a transformative approach against HIV.Molecular biology reports · 2026Review
- PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease.Nature reviews. Rheumatology · 2026Review
- The role of programmed cell death 1 in autoimmune diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Tumor organoid-immune cell co-culture systems for precision oncology.Frontiers in cell and developmental biology · 2026Review
- Engineered extracellular vesicles reprogram T cells by targeting PD-1 and PHB1 signaling in inflammatory bowel disease.Signal transduction and targeted therapy · 2025Article
- Exosomal regulation of cellular reprogramming and polarization in the tumor microenvironment.Cancer cell international · 2025Review
- Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices.bioRxiv : the preprint server for biology · 2025Article
- Nanomedicine targeting the PD-1/PD-L1 axis in autoimmune diseases: breaking conventional barriers to restore immune tolerance.Journal of nanobiotechnology · 2025Review
- Regulatory T cell and endothelial cell crosstalk.Nature reviews. Immunology · 2025Review
- Utilizing miR-34a-Loaded HER2-Targeting Exosomes to Improve Breast Cancer Treatment: Insights From an Animal Model.Journal of breast cancer · 2025Article
- Extracellular Vesicles and PD-L1-A Review of Complex Immunoregulatory Properties and Clinical Importance.Biomedicines · 2025Review
- Improved acid-driven inhibition of effector T cell function by a pHLIP variant-conjugated PD-L1.Scientific reports · 2025Article
- Mechanisms and therapeutic strategies to reveal and overcome T-cell dysfunction in gastric cancer: translation from basic research to clinical application.Frontiers in immunology · 2025Review
- Therapeutic implications for the PD-1 axis in cerebrovascular injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Immune inhibitory receptor agonist therapeutics.Frontiers in immunology · 2025Review
- Development of a prediction model integrating PD-1 and ICOS for early differential diagnosis between autoimmune and viral encephalitis.Frontiers in immunology · 2025Article
- Cell-targeted PD-1 agonists are potent NK-cell inhibitors.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
23 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PD-1/PD-L1 pathway is a key immune checkpoint that regulates T cell activation. There is strong rationale to develop PD-1 agonists as therapeutics against autoimmunity, but progress in this area has been limited. Here, we generated T cell receptor (TCR) targeting, PD-1 agonist bispecifics called ImmTAAI molecules that mimic the ability of PD-L1 to facilitate the colocalization of PD-1 with the TCR complex at the target cell-T cell interface. PD-1 agonist ImmTAAI molecules specifically bound to target cells and were highly effective in activating the PD-1 receptor on interacting T cells to achieve immune suppression. Potent PD-1 antibody ImmTAAI molecules closely mimicked the mechanism of action of endogenously expressed PD-L1 in their localization to the target cell-T cell interface, inhibition of proximal TCR signaling events, and suppression of T cell function. At picomolar concentrations, these bispecifics suppressed cytokine production and inhibited CD8+ T cell-mediated cytotoxicity in vitro. Crucially, in soluble form, the PD-1 ImmTAAI molecules were inactive and, hence, could avoid systemic immunosuppression. This study outlines a promising new route to generate more effective, potent, tissue-targeted PD-1 agonists that can inhibit T cell function locally with the potential to treat autoimmune and chronic inflammatory diseases of high unmet need.
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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.