ArticleNature communications2025
Modeling and addressing on-target/off-tumor toxicity of claudin 18.2 targeted immunotherapies.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed.
- Clinical implications of zolbetuximab-associated hypoalbuminemia in CLDN18.2-positive gastric or gastroesophageal junction cancer.ESMO gastrointestinal oncology · 2026Article
- Clinician and patient attitudes toward locoregional treatment of oligometastatic oesophago-gastric cancers: a mixed-methods study.ESMO gastrointestinal oncology · 2026Article
- Claudin-18.2 in Gastric and Gastroesophageal Junction Adenocarcinoma: From Biology to Therapeutic Targeting: A Narrative Review.Targeted oncology · 2026Review
- Nanobody-based targeted cancer therapy and immunotherapy: fear not the future.Acta pharmacologica Sinica · 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
- Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.Signal transduction and targeted therapy · 2026Review
- The global clinical trial landscape of lung cancer cellular therapy current status trends and scientific challenges.Discover oncology · 2026Article
- Claudin18.2 positive gastric cancer: biology, tumor microenvironment, and therapeutic strategies.Journal of hematology & oncology · 2026Review
- GPA33 forms a distinct diagnostic target class to Claudin 18.2 in oesophageal adenocarcinoma enabling the development of a novel GPA33 antibody-based detection platform.Cellular & molecular biology letters · 2026Article
- CLDN18.2-Directed Therapeutics in Gastric and Gastroesophageal Junction Adenocarcinoma: Biomarker Assessment, Expression Dynamics, and Treatment Sequencing.Cancer management and research · 2026Review
- Glucan-Based Nanoparticles Empower Precision Cancer Immunotherapy: Design Strategies, Immune Reprogramming Mechanisms, and Clinical Translation Prospects.International journal of nanomedicine · 2026Review
- Safety signals of zolbetuximab in gastric or gastroesophageal junction adenocarcinoma: a comprehensive analysis of the FDA adverse event reporting system (FAERS) data.Frontiers in oncology · 2026Article
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
- CLDN18.2 in Gastric Cancer: Current Therapeutic Landscape and Future Perspectives.Journal of gastric cancer · 2026Review
- Safety and efficacy of zolbetuximab plus chemotherapy for claudin 18 isoform 2-positive advanced gastric cancer: initial report of real-world experience.Journal of cancer research and clinical oncology · 2025Article
- Multi-Omics-Enabled Precision Strategies for Overcoming CAR-T Therapy Limitations in Gastrointestinal Malignancies.BioFactors (Oxford, England)Review
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Successfully extending immunotherapies to solid tumors involves addressing several key challenges, importantly the "antigen dilemma", the expression of a solid tumor target antigen on the normal tissue of tumor origin. Claudin 18.2 (CLDN18.2) has emerged as an important target for upper gastrointestinal (GI) cancer therapies (such as Zolbetuximab, a naked antibody, recently approved; or CT041, a second-generation chimeric antigen receptor (CAR) T cell therapy with promising clinical data). However, GI toxicities are reported from clinical use of both Zolbetuximab and CT041. Here, we describe clinical Zolbetuximab treatment associated cases of gastric erosive lesions. We also demonstrate and characterize on-target/off-tumor gastric toxicity targeting CLDN18.2 in a preclinical mouse model of CT041-scFv derived CAR T cell therapy. By developing CLDN18.2 fully-human VH-only single domain CARs, we demonstrate that on-target/off-tumor toxicity inversely correlates with affinity of the binder, and that a lower affinity CAR may widen the therapeutic window for CLDN18.2 by decreasing on-target/off-tumor toxicity while preserving efficacy.
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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.