ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Anti-PD-1/Her2 Bispecific Antibody IBI315 Enhances the Treatment Effect of Her2-Positive Gastric Cancer through Gasdermin B-Cleavage Induced Pyroptosis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 47 citations in OpenAlex.
- Review
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Gastric Cancer Organoids: Mechanistic Insights, Drug Discovery, and Translational Advances in Precision Medicine.Journal of gastric cancer · 2026Review
- The molecular mechanisms of pyroptosis and its implications in tumor immunotherapy.Molecular cancer · 2026Review
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- Patient-derived organoids in gastric cancer: bridging the tumor microenvironment to functional precision oncology.Frontiers in bioengineering and biotechnology · 2026Review
- The relationship between gut microbiota and cancer immune response and immunotherapy.Frontiers in immunology · 2026Review
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
- Monoclonal Antibodies and Derivatives: Therapeutic Tools for Cancer.Oncology research · 2026Review
- A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers.Oncology research · 2026Review
- Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression.Molecular cancer · 2025Review
- Cracking the code of cancer immunotherapy resistance: emerging roles of pyroptosis and necroptosis.Journal of experimental & clinical cancer research : CR · 2025Review
- Research advancements and evaluation of multifactor-induced murine models for gastric cancer.Animal models and experimental medicine · 2025Review
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- Anti-CTGF/PD-1 bispecific antibody Y126S restrains desmoplastic and immunosuppressive microenvironment in pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications.Biomolecules · 2025Review
- Multispecific Antibodies Targeting PD-1/PD-L1 in Cancer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Evolving Landscape of HER2-Targeted Therapies for Gastric Cancer Patients.Current treatment options in oncology · 2025Review
- Preclinical study of inetetamab combined with atezolizumab to synergistically inhibit HER2 and PD-L1 in the treatment of ovarian cancer.Molecular therapy. Oncology · 2025Article
- Leveraging immune checkpoint inhibitors in lung cancer patients with pre-existing autoimmune disease: clinical insights, optimal timing, and predictive biomarkers for optimal treatment outcomes.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
The majority of patients with human epidermal growth factor receptor 2 (Her2)-positive gastric cancer develop refractory to Her2-targeted therapy, where upregulation of immune checkpoints plays an essential role. Herein, a recombinant fully human IgG1 bispecific antibody IBI315 targeting both PD-1 and Her2 is developed and its antitumor efficacy as well as the underlying mechanism is investigated. IBI315 crosslinks the physical interaction between Her2-positive tumor cells and PD-1-positive T cells, resulting in significantly enhanced antitumor effects compared to each parent antibody or their combination, both in vitro and in vivo mouse tumor models reconstituted with human immune cells using patient-derived xenografts and organoids. Moreover, IBI315 treatment also induces the recruitment and activation of immune cells in tumors. Mechanistically, IBI315 triggers gasdermin B (GSDMB)-mediated pyroptosis in tumor cells, leading to the activation and recruiments of T cells. The activated T cells secret IFNγ, enhancing GSDMB expression and establishing a positive feedback loop of T cell activation and tumor cell killing. Notably, GSDMB is found to be elevated in Her2-positive gastric cancer cells, providing a rationale for IBI315's efficacy. IBI315 is supported here as a promising bispecific antibody-based immunotherapy approach for Her2-positive gastric cancer in preclinical studies, broadening the therapeutic landscape of this patient population.
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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.