ArticleBritish journal of cancer2023
Rational design of PD-1-CD28 immunostimulatory fusion proteins for CAR T cell therapy.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Multifunctional-engineered NK cells overcome tumor immunosuppression by combining PD-L1 and HLA-E targeting and endogenous IL15 production.Signal transduction and targeted therapy · 2026Article
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- Unlocking the potential: current landscape and future directions of immunotherapy in gastric cancer.Frontiers in immunology · 2026Review
- Recent advances and challenges of cellular immunotherapies in lung cancer treatment.Experimental hematology & oncology · 2025Review
- Multiplex engineering and multifunction T cells for precise and effective immunotherapies.Frontiers in immunology · 2025Review
- Immunotherapy in metastatic prostate cancer.Therapeutic advances in medical oncology · 2025Review
- Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release.Cancers · 2024Article
- Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector.Journal of microbiology (Seoul, Korea) · 2024Article
- Targeting KIR as a novel approach to improve CAR-NK cell function.Journal of translational genetics and genomics · 2023Article
- Progress of research on PD-1/PD-L1 in leukemia.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn many situations, the therapeutic efficacy of CAR T cells is limited due to immune suppression and poor persistence. Immunostimulatory fusion protein (IFP) constructs have been advanced as a tool to convert suppressive signals into stimulation and thus promote the persistence of T cells, but no universal IFP design has been established so far. We now took advantage of a PD-1-CD28 IFP as a clinically relevant structure to define key determinants of IFP activity.
methodsWe compared different PD-1-CD28 IFP variants in a human leukemia model to assess the impact of distinctive design choices on CAR T cell performance in vitro and a xenograft mouse model.
resultsWe observed that IFP constructs that putatively exceed the extracellular length of PD-1 induce T-cell response without CAR target recognition, rendering them unsuitable for tumour-specific therapy. IFP variants with physiological PD-1 length ameliorated CAR T cell effector function and proliferation in response to PD-L1
conclusionPD-1-CD28 IFP constructs must mimic the physiological interaction of PD-1 with PD-L1 to retain selectivity and mediate CAR-conditional therapeutic activity.
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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.