ArticleNature communications2019
Engineered triple inhibitory receptor resistance improves anti-tumor CAR-T cell performance via CD56.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
What it found
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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.
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Who cites it
77 citing papers in PubMed, 118 citations in OpenAlex.
- PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Trial
- Augmenting CAR T cell functionality and metabolism through CD39 downtuning.Molecular therapy. Oncology · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Shuangshen granules enhance anti-PD1 therapy effectiveness in lung adenocarcinoma by modulating myeloid-derived suppressor cell-induced T cell exhaustion.Chinese medicine · 2026Article
- PD-L1-Binding Antigen Presenters: Redirecting Vaccine-Induced Antibodies for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic editing to advance CAR T cell therapy.Clinical epigenetics · 2026Review
- FAM168B identified as a novel candidate target for chimeric antigen receptor T cell-based cancer therapy.Discover oncology · 2026Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Harnessing cellular immunotherapy for cholangiocarcinoma: an integrated roadmap for overcoming resistance.Frontiers in immunology · 2026Review
- Review
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.Nature reviews. Clinical oncology · 2025Review
- Protein catenation potentiates antitumor activity of malaria VAR2CSA navigation CAR-T cells in a mouse model of hematological malignancies.Journal for immunotherapy of cancer · 2025Article
- Triple checkpoint blockade of PD-1, Tim-3, and Lag-3 enhances adoptive T cell immunotherapy in a mouse model of ovarian cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Selinexor Reduces the Immunosuppression of Macrophages and Synergizes With CD19 CAR-T Cells Against B-Cell Lymphoma.Cancer science · 2025Article
- Chimeric Antigen Receptor Immunotherapy for Infectious Diseases: Current Advances and Future Perspectives.Pathogens (Basel, Switzerland) · 2025Review
- Recent advances and challenges of cellular immunotherapies in lung cancer treatment.Experimental hematology & oncology · 2025Review
- Surface downmodulation of TIM3 safeguards healthy cells but not acute myeloid leukemia from CAR T-cell therapy.HemaSphere · 2025Article
- CAR-Based Cell Therapy in Head and Neck Cancer: A Comprehensive Review on Clinical Applicability.Cancers · 2025Review
- Enhanced anti-tumor activity by zinc finger repressor-driven epigenetic silencing of immune checkpoints and TGFBR2 in CAR-T cells and TILs.Molecular therapy. Oncology · 2025Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibitory receptors PD-1, Tim-3, and Lag-3 are highly expressed on tumor-infiltrating lymphocytes and compromise their antitumor activity. For efficient cancer immunotherapy, it is important to prevent chimeric antigen receptor T (CAR-T)-cell exhaustion. Here we downregulate these three checkpoint receptors simultaneously on CAR-T cells and that show the resulting PTL-CAR-T cells undergo epigenetic modifications and better control tumor growth. Furthermore, we unexpectedly find increased tumor infiltration by PTL-CAR-T cells and their clustering between the living and necrotic tumor tissue. Mechanistically, PTL-CAR-T cells upregulate CD56 (NCAM), which is essential for their effector function. The homophilic interaction between intercellular CD56 molecules correlates with enhanced infiltration of CAR-T cells, increased secretion of interferon-γ, and the prolonged survival of CAR-T cells. Ectopically expressed CD56 promotes CAR-T cell survival and antitumor response. Our findings demonstrate that genetic blockade of three checkpoint inhibitory receptors and the resulting high expression of CD56 on CAR-T cells enhances the inhibition of tumor growth.
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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.