ArticleScientific reports2022
Combination gemcitabine and PD-L1xCD3 bispecific T cell engager (BiTE) enhances T lymphocyte cytotoxicity against cholangiocarcinoma cells.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Blockage of cuproplasia inhibits pancreatic tumour-associated neutrophils infiltration through TRAF6/STAT3/CCL2 pathway.British journal of cancer · 2026Article
- CAR-T cells directed toward PD-L1 demonstrate potent, antigen-specific activity against cholangiocarcinoma: A proof of concept study.Molecular therapy. Oncology · 2026Article
- Recent Advances in Pancreatic Cancer and Biliary Tract Cancers: Biology, Biomarkers, and Evolving Systemic Therapy.International journal of molecular sciences · 2026Review
- Current Status of Drug Treatment of Cholangiocarcinoma-Updated Progress and Critical Limitations.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Harnessing a bispecific αGD2 × αCD3 protein engager to target GD2-overexpressing lung tumors.Scientific reports · 2026Article
- A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers.Oncology research · 2026Review
- Docetaxel enhances Vβ-directed T-cell activation and antitumor immunity mediated by a bifunctional TCR agonist in breast and prostate cancer models.Frontiers in immunology · 2026Article
- 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
- Research progress of T cells in cholangiocarcinoma.Frontiers in immunology · 2025Review
- Bispecific Siglec-15/T cell antibody (STAB) activates T cells and suppresses pancreatic ductal adenocarcinoma and non-small cell lung tumorsTheranostics · 2025Article
- Targeting PD-L1 in cholangiocarcinoma using nanovesicle-based immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Tri-specific killer engager: unleashing multi-synergic power against cancer.Exploration of targeted anti-tumor therapy · 2024Review
- Polysaccharide extract of Spirulina sp. increases effector immune-cell killing activities against cholangiocarcinoma.PloS one · 2024Article
- Immunobiology of cholangiocarcinoma.Journal of hepatology · 2023Review
- BiTE-Secreting CAR-γδT as a Dual Targeting Strategy for the Treatment of Solid Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Immunology and immunotherapy of cholangiocarcinoma.Nature reviews. Gastroenterology & hepatology · 2023Review
- Radiation-induced tumor immune microenvironments and potential targets for combination therapy.Signal transduction and targeted therapy · 2023Review
- Activation of T Lymphocytes with Anti-PDL1-BiTE in the Presence of Adipose-Derived Mesenchymal Stem Cells (ASCs).BioMed research international · 2023Article
- Combination therapies for the optimisation of Bispecific T-cell Engagers in cancer treatment.Immunotherapy advances · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholangiocarcinoma (CCA) is a lethal cancer with rapid progression and poor survival. Novel and more effective therapies than those currently available are, therefore, urgently needed. Our research group previously reported the combination of gemcitabine and cytotoxic T lymphocytes to be more effective than single-agent treatment for the elimination of CCA cells. However, gemcitabine treatment of CCA cells upregulates the expression of an immune checkpoint protein (programmed death-ligand 1 [PD-L1]) that consequently inhibits the cytotoxicity of T lymphocytes. To overcome this challenge and take advantage of PD-L1 upregulation upon gemcitabine treatment, we generated recombinant PD-L1xCD3 bispecific T cell engagers (BiTEs) to simultaneously block PD-1/PD-L1 signaling and recruit T lymphocytes to eliminate CCA cells. Two recombinant PD-L1xCD3 BiTEs (mBiTE and sBiTE contain anti-PD-L1 scFv region from atezolizumab and from a published sequence, respectively) were able to specifically bind to both CD3 on T lymphocytes, and to PD-L1 overexpressed after gemcitabine treatment on CCA (KKU213A, KKU055, and KKU100) cells. mBiTE and sBiTE significantly enhanced T lymphocyte cytotoxicity against CCA cells, especially after gemcitabine treatment, and their magnitudes of cytotoxicity were positively associated with the levels of PD-L1 expression. Our findings suggest combination gemcitabine and PD-L1xCD3 BiTE as a potential alternative therapy for CCA.
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