ArticleCancer communications (London, England)2023
Enhancement of CAR-T cell activity against cholangiocarcinoma by simultaneous knockdown of six inhibitory membrane proteins.
Article in Cancer communications (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 45 citations in OpenAlex.
- First-line tislelizumab and ociperlimab combined with gemcitabine and cisplatin in advanced biliary tract cancer (ZSAB-TOP): a multicenter, single-arm, phase 2 study.Signal transduction and targeted therapy · 2025Trial
- Extracellular vesicle proteins monitor and interfere with CLDN18.2-targeted CAR-T cell and antibody therapies against gastrointestinal cancers.Nature communications · 2026Article
- Advances and challenges in immunotherapy for intrahepatic cholangiocarcinoma based on the tumour immune microenvironment.Clinical and translational medicine · 2026Review
- B7-H3 CAR T cells eradicate intrahepatic cholangiocarcinoma and induce durable response.Journal of experimental & clinical cancer research : CR · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- PD-L1-Binding Antigen Presenters: Redirecting Vaccine-Induced Antibodies for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Harnessing cellular immunotherapy for cholangiocarcinoma: an integrated roadmap for overcoming resistance.Frontiers in immunology · 2026Review
- Organoid models: reshaping the paradigm for precision development and evaluation of CAR-T cell therapies.Frontiers in bioengineering and biotechnology · 2026Review
- Overcoming heterogeneity and immunosuppression: novel strategies in adoptive therapy for biliary tract cancer.Frontiers in immunology · 2026Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- Research progress on immune checkpoint inhibitors in intrahepatic cholangiocarcinoma.Annals of medicine · 2025Review
- TIGIT blockade in the context of BCMA-CART cell therapy does not augment efficacy in a multiple myeloma mouse model.Oncoimmunology · 2025Article
- Asparaginase enhances CAR-T cell antitumor immunity by asparagine metabolic reprogramming and central memory induction in ALL.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- Recent advances and challenges of cellular immunotherapies in lung cancer treatment.Experimental hematology & oncology · 2025Review
- Development of CAR-T Therapies and Personalized Vaccines for the Treatment of Cholangiocarcinoma: Current Progress, Mechanisms of Action, and Challenges.The American journal of pathology · 2025Review
- Chimeric antigen receptor T-cell therapy in patients with malignant glioma-From neuroimmunology to clinical trial design considerations.Neuro-oncology · 2025Review
- Research progress of T cells in cholangiocarcinoma.Frontiers in immunology · 2025Review
- Advancing biliary tract malignancy treatment: emerging frontiers in cell-based therapies.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExisting treatments for cholangiocarcinoma have poor efficacy. However, chimeric antigen receptor-T (CAR-T) cells are emerging as a potential therapeutic strategy. Solid tumors possess multiple adverse factors in an immunosuppressive microenvironment that impair CAR-T cell infiltration and function. This study aimed to improve the function of CAR-T cells through knock down immune checkpoints and immunosuppressive molecular receptors.
methodsWe evaluated the expression of epidermal growth factor receptor (EGFR) and B7 homolog 3 protein (B7H3) antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry. Subsequently, we engineered CAR-T cells targeting EGFR and B7H3 antigens. We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR-T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR-T cells for antitumor activity both in vitro, using tumor cell lines and cholangiocarcinoma organoid models, and in vivo, using humanized mouse models.
resultsWe observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues. EGFR-CAR-T and B7H3-CAR-T cells demonstrated specific anti-tumor activity. We found an abundance of programmed cell death protein 1 (PD-1), T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), and T cell immunoglobulin and ITIM domain (Tigit) on infiltrated CD8
conclusionsOur results revealed that PTG-T16R-scFV-CAR-T cells with knockdown of sextuplet inhibitory molecules exhibited strong immunity against cholangiocarcinoma and long-term efficacy both in vitro and in vivo. This strategy provides an effective and personalized immune cell therapy against cholangiocarcinoma.
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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.