ArticleImmunity2023
Deletion of the inhibitory co-receptor CTLA-4 enhances and invigorates chimeric antigen receptor T cells.
Article in Immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.
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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
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Clinical Impact of CTLA4 and LAG3 Single-Nucleotide Polymorphisms in Multiple Myeloma Patients Treated With BCMA CAR T-Cell Therapy.Hematological oncology · 2026Article
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- Augmenting CAR T cell functionality and metabolism through CD39 downtuning.Molecular therapy. Oncology · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Dual-modular-nanobody CAR-T cell technical platform against the solid tumor microenvironment.Journal of hematology & oncology · 2026Article
- Endogenous CD28 takes the driver's seat in 4-1BB co-stimulated CAR T cells.Molecular therapy. Oncology · 2026Article
- Exosomes liquid biopsy in Lymphoma precision medicine: applications and challenges.Cancer cell international · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Article
- Challenges and advances in CAR-T cell therapy for B-ALL.Biomarker research · 2026Review
- Computational identification of migrating T cells in spatial transcriptomics data.JCI insight · 2026Article
- Endogenous CD28 Drives the Persistent Activity of CAR T Cells in Myeloma and Lymphoma Models.Blood cancer discovery · 2026Article
- Engineered outer membrane vesicles enhance solid tumour CAR-T cell therapy.Nature biomedical engineering · 2026Article
- Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.International journal of molecular sciences · 2026Review
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- Teriflunomide modulates the PD-1/PD-L1 axis and enhances antitumor immunity in colorectal cancer.Oncogenesis · 2026Article
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- TIGIT Blockade Potentiates the Anti-Leukemic Activity of Exercise-Mobilized Donor Lymphocytes and Expanded γδ T-Cells.Cancers · 2026Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has achieved tremendous success treating B cell malignancies; however, some patients fail to respond due to poor autologous T cell fitness. To improve response rates, we investigated whether disruption of the co-inhibitory receptors CTLA4 or PD-1 could restore CART function. CRISPR-Cas9-mediated deletion of CTLA4 in preclinical models of leukemia and myeloma improved CAR T cell proliferation and anti-tumor efficacy. Importantly, this effect was specific to CTLA4 and not seen upon deletion of CTLA4 and/or PDCD1 in CAR T cells. Mechanistically, CTLA4 deficiency permitted unopposed CD28 signaling and maintenance of CAR expression on the T cell surface under conditions of high antigen load. In clinical studies, deletion of CTLA4 rescued the function of T cells from patients with leukemia that previously failed CAR T cell treatment. Thus, selective deletion of CTLA4 reinvigorates dysfunctional chronic lymphocytic leukemia (CLL) patient T cells, providing a strategy for increasing patient responses to CAR T cell therapy.
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Registered trials
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.