ArticleNature biomedical engineering2024
Analysis of off-tumour toxicities of T-cell-engaging bispecific antibodies via donor-matched intestinal organoids and tumouroids.
Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 65 citations in OpenAlex.
- On-chip 3D potency assay for prediction of clinical outcomes for cell therapy candidates for osteoarthritis.Nature communications · 2025Trial
- Human lung explants as a predictive platform for evaluating the on-target, off-tumor toxicity of T cell bispecifics.iScience · 2026Article
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Construction Strategies, Microenvironmental Modelling and Precision-Therapy Applications of Glioma Organoid Models.Cancers · 2026Review
- Next-generation skin wound healing related disease models with integration of immune cells.Protein & cell · 2026Review
- From T cell engagers to next-generation immune cell engagers for cancer immunotherapy.Antibody therapeutics · 2026Review
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Organoid technology in cancer research.Molecular biomedicine · 2026Review
- High-throughput histopathology for complex in vitro models.Cell reports methods · 2026Article
- Tumor organoids as a revolutionary platform for advancing cancer nanomedicine.Molecular cancer · 2026Review
- Tumor organoid platform design for drug response modeling: culture architecture, microenvironmental complexity, and AI-assisted readouts.Archives of pharmacal research · 2026Review
- Single-Cell Protein Assays in Context: From 2D to 3D and In Situ Analysis.Annual review of analytical chemistry (Palo Alto, Calif.) · 2026Review
- Allogeneic Immune Cell Perfusion Inhibits the Growth of Vascularized 3D In Vitro Tumor Models, Induces Vascular Regression and Desmoplasia, but Promotes Tumor Cell Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated Microfluidic Platform for High-Throughput Generation of Intestinal Organoids in Hydrogel Droplets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges.Nature reviews. Drug discovery · 2026Review
- Organoids in drug development: from predictive models to regulatory integration.Drug discovery today · 2026Review
- Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in multiple cancer types.Experimental hematology & oncology · 2026Review
- Probiotic-inspired hybrid nanovesicles for enhancing immune checkpoint therapy efficiency via tumor immune microenvironment modulation.Bioactive materials · 2026Article
- A New Paradigm of Bispecific Antibodies in Clinical Management of Gastrointestinal Cancers.Oncology research · 2026Review
- Mitochondrial gatekeeper in hepatocellular carcinoma: Unraveling the multifaceted roles of VDAC in metabolic reprogramming, apoptosis evasion and therapeutic innovation (Review).Molecular medicine reports · 2026Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Predicting the toxicity of cancer immunotherapies preclinically is challenging because models of tumours and healthy organs do not typically fully recapitulate the expression of relevant human antigens. Here we show that patient-derived intestinal organoids and tumouroids supplemented with immune cells can be used to study the on-target off-tumour toxicities of T-cell-engaging bispecific antibodies (TCBs), and to capture clinical toxicities not predicted by conventional tissue-based models as well as inter-patient variabilities in TCB responses. We analysed the mechanisms of T-cell-mediated damage of neoplastic and donor-matched healthy epithelia at a single-cell resolution using multiplexed immunofluorescence. We found that TCBs that target the epithelial cell-adhesion molecule led to apoptosis in healthy organoids in accordance with clinical observations, and that apoptosis is associated with T-cell activation, cytokine release and intra-epithelial T-cell infiltration. Conversely, tumour organoids were more resistant to damage, probably owing to a reduced efficiency of T-cell infiltration within the epithelium. Patient-derived intestinal organoids can aid the study of immune-epithelial interactions as well as the preclinical and clinical development of cancer immunotherapies.
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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.