ArticleGastroenterology2023
CLDN18.2 BiTE Engages Effector and Regulatory T Cells for Antitumor Immune Response in Preclinical Models of Pancreatic Cancer.
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Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
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Who cites it
25 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting KRAS reprograms a Treg-dominant immunosuppressive microenvironment and sensitizes KRAS-mutant gastric adenocarcinoma to CTLA-4 immunotherapy.Science China. Life sciences · 2026Article
- Research Progress and Optimization Strategies of Bispecific Antibody Therapies for CLDN18.2-Positive Gastric Cancer.Journal of gastrointestinal cancer · 2026Review
- Targeting claudins in cancer.Nature reviews. Drug discovery · 2026Review
- Progress in the application ofAnnals of nuclear medicine · 2026Review
- Clinical overall survival prediction and disease characteristics of locally advanced non-small cell lung cancer: an integrated analysis based on the SEER and TCGA databases.Translational cancer research · 2026Article
- Claudin18.2 and the PD-1/PD-L1 axis in gastric cancer: mechanistic insights and implications for combination immunotherapy.Journal of translational medicine · 2026Review
- CXCR2 blockade overcomes the NETosis-mediated resistance to MEK inhibition in pancreatic cancer models.The Journal of clinical investigation · 2026Article
- Claudin proteins as emerging therapeutic targets for solid tumours.Nature reviews. Cancer · 2026Review
- Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.Journal of hematology & oncology · 2026Review
- Research progress on the influence of tumor microenvironment on immunotherapy for pancreatic ductal adenocarcinoma.Open medicine (Warsaw, Poland) · 2026Review
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
- The tumour microenvironment in pancreatic cancer - new clinical challenges, but more opportunities.Nature reviews. Clinical oncology · 2025Review
- Novel Claudin18.2-Targeted Therapies in Gastrointestinal Tumors.ACS omega · 2025Review
- Biomimetic Tumour Model Systems for Pancreatic Ductal Adenocarcinoma in Relation to Photodynamic Therapy.International journal of molecular sciences · 2025Review
- LIM domain only 7: a novel driver of immune evasion through regulatory T cell differentiation and chemotaxis in pancreatic ductal adenocarcinoma.Cell death and differentiation · 2025Article
- ATR inhibition potentiates FOLFIRINOX cytotoxic effect in models of pancreatic ductal adenocarcinoma by remodelling the tumour microenvironment.British journal of cancer · 2025Article
- Bispecific Siglec-15/T cell antibody (STAB) activates T cells and suppresses pancreatic ductal adenocarcinoma and non-small cell lung tumorsTheranostics · 2025Article
- Article
- Mechanistic insights into resistance mechanisms to T cell engagers.Frontiers in immunology · 2025Review
- Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review).International journal of molecular medicine · 2024Review
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Authors and funding
25 authors at 3 institutions in 2 countries.
Yao XuThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Juan FuThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
MacKenzie HendersonThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Fei LeeOncology Research, Amgen Research, Amgen, Inc, South San Francisco, California.
Noelle JurcakThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Anja HennTranslational Safety and Bioanalytical Sciences, Amgen Research (Munich) GmbH, Munich, Germany.
Joachim WahlTranslational Safety and Bioanalytical Sciences, Amgen Research (Munich) GmbH, Munich, Germany.
Yingkuan ShaoThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jianxin WangThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Melissa LymanThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Vanessa FunesThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Birginia EspinozaThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Rui ZhangThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
India WashingtonThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Sophia Y ChenThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Haley ZlomkeThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Junke WangThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Nan NiuThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Pan LiThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Fengxi MengThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
William BurnsThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Matthias FriedrichTranslational Safety and Bioanalytical Sciences, Amgen Research (Munich) GmbH, Munich, Germany.
Sabine StienenClinical Development, Amgen Research (Munich) GmbH, Munich, Germany.
Julie M BailisOncology Research, Amgen Research, Amgen, Inc, South San Francisco, California. Electronic address: jbailis@amgen.com.
Lei ZhengThe Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland; The Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: lzheng6@jhmi.edu.
Bloomberg (United States) · USAmgen (Germany) · DEAmgen (United States) · US
Funding
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6MTransforming Human Pancreatic Cancer Into An Immunologic DiseaseP01CA247886 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANDERS, ROBERT A. · 2021 to 2025
$12.7MTargeting the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer with a Neoadjuvant Platform Clinical TrialR01CA197296 · NCI · JOHNS HOPKINS UNIVERSITY · PI William Reece Burns, Eric Christenson · 2015 to 2026
$5.7MInterrogate the interaction between tumor cells and nerves in the tumor microenvironment of pancreatic cancerR01CA169702 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI ZHENG, LEI · 2013 to 2023
$3.6MNCI NIH HHS P01 CA247886NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA169702NCI NIH HHS R01 CA197296
Abstract
BACKGROUND &
aimsBiTE (bispecific T-cell engager) immune therapy has demonstrated clinical activity in multiple tumor indications, but its influence in the tumor microenvironment remains unclear. CLDN18.2 is overexpressed in solid tumors including gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC), both of which are characterized by the presence of immunosuppressive cells, including regulatory T cells (Tregs) and few effector T cells (Teffs).
methodsWe evaluated the activity of AMG 910, a CLDN18.2-targeted half-life extended (HLE) BiTE molecule, in GC and PDAC preclinical models and cocultured Tregs and Teffs in the presence of CLDN18.2-HLE-BiTE.
resultsAMG 910 induced potent, specific cytotoxicity in GC and PDAC cell lines. In GSU and SNU-620 GC xenograft models, AMG 910 engaged human CD3
conclusionsOur data suggest that BiTE molecule treatment converts Treg function from immunosuppressive to immune enhancing, leading to antitumor activity in immunologically "cold" tumors.
Indexed as
Antibodies, BispecificCarcinoma, Pancreatic DuctalPancreatic NeoplasmsAnimalsCell Adhesion MoleculesClaudinsHumansImmunityMiceT-Lymphocytes, RegulatoryTumor MicroenvironmentAntibodies, BispecificCell Adhesion MoleculesClaudinsCLDN18 protein, humanBispecific AntibodyImmune Checkpoint BlockadeRNA Sequencing
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