ArticleEBioMedicine2017
Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy.
Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05119010 (A Pilot Study Evaluating a Ketogenic Diet Concomitant to Nivolumab and Ipilimumab in Patients With Metastatic Renal Cell Carcinoma), which is not on this map. Cited by 30 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.
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.
A Pilot Study Evaluating a Ketogenic Diet Concomitant to Nivolumab and Ipilimumab in Patients With Metastatic Renal Cell Carcinoma
Who cites it
30 citing papers in PubMed.
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- In Search of Better Peptide-(Derived from PD-L2)-Based Immune Checkpoint Inhibitors.Biomolecules · 2024Article
- Balancing the Nanoscale Organization in Multivalent Materials for Functional Inhibition of the Programmed Death-1 Immune Checkpoint.ACS nano · 2024Article
- Programmed cell death-ligand 2: new insights in cancer.Frontiers in immunology · 2024Review
- PD-1 immunology in the kidneys: a growing relationship.Frontiers in immunology · 2024Review
- Development of an Albumin-Masked mutPD-1Ig as a Tumor Lesion-Selective Immune Checkpoint Inhibitor.ACS omega · 2023Article
- The role of PD-1 signaling in health and immune-related diseases.Frontiers in immunology · 2023Review
- CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity.PloS one · 2023Article
- Pan-cancer analysis identifies PD-L2 as a tumor promotor in the tumor microenvironment.Frontiers in immunology · 2023Article
- Role of IL-18-transformed CD274-expressing eosinophils in promoting airway obstruction in experimental asthma.Allergy · 2022Article
- Dynamic proteomic change of tumor and immune organs in an immune-competent hepatocellular carcinoma mouse model.American journal of cancer research · 2022Article
- IL-10 Signaling Elicited by Nivolumab-Induced Activation of the MAP Kinase Pathway Does Not Fully Contribute to Nivolumab-Modulated Heterogeneous T Cell Responses.International journal of molecular sciences · 2021Article
- Emerging concepts in PD-1 checkpoint biology.Seminars in immunology · 2021Review
- Understanding the Targeting Mechanisms of Multi-Specific Biologics in Immunotherapy with Multiscale Modeling.iScience · 2020Article
- Virtual Screening and In Vitro Evaluation of PD-1 Dimer Stabilizers for Uncoupling PD-1/PD-L1 Interaction from Natural Products.Molecules (Basel, Switzerland) · 2020Article
- Revisiting the PD-1 pathway.Science advances · 2020Review
- Review
- Preparation of Biphenyl-Conjugated Bromotyrosine for Inhibition of PD-1/PD-L1 Immune Checkpoint Interactions.International journal of molecular sciences · 2020Article
- Assessment of hazard immune-related genes and tumor immune infiltrations in renal cell carcinoma.American journal of translational research · 2020Article
- T cell costimulation, checkpoint inhibitors and anti-tumor therapy.Journal of biosciences · 2020Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Programmed Cell Death-1 (PD-1) is an inhibitory immune receptor, which plays critical roles in T cell co-inhibition and exhaustion upon binding to its ligands PD-L1 and PD-L2. We report the crystal structure of the human PD-1 ectodomain and the mapping of the PD-1 binding interface. Mutagenesis studies confirmed the crystallographic interface, and resulted in mutant PD-1 receptors with altered affinity and ligand-specificity. In particular, a high-affinity mutant PD-1 (HA PD-1) exhibited 45 and 30-fold increase in binding to PD-L1 and PD-L2, respectively, due to slower dissociation rates. This mutant (A132L) was used to engineer a soluble chimeric Ig fusion protein for cell-based and in vivo studies. HA PD-1 Ig showed enhanced binding to human dendritic cells, and increased T cell proliferation and cytokine production in a mixed lymphocyte reaction (MLR) assay. Moreover, in an experimental model of murine Lewis lung carcinoma, HA PD-1 Ig treatment synergized with radiation therapy to decrease local and metastatic tumor burden, as well as in the establishment of immunological memory responses. Our studies highlight the value of structural considerations in guiding the design of a high-affinity chimeric PD-1 Ig fusion protein with robust immune modulatory properties, and underscore the power of combination therapies to selectively manipulate the PD-1 pathway for tumor immunotherapy.
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Registered trials
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