ArticleMolecular cancer therapeutics2022
Anti-Extra Domain B Splice Variant of Fibronectin Antibody-Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Extracellular payload release from non-internalizing antibody-drug conjugates: mechanisms and linker technologies.Drug delivery · 2026Review
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- A Living Multi-Omics PDX Biobank of High-Risk Sarcomas Reveals ecDNA-Driven Oncogene Amplification in Osteosarcoma and Enables Preclinical Precision Oncology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026Review
- From Unmet Medical Need to Drug Candidate: A Translational Therapeutic Development Roadmap Illustrated by Dual-Payload Antibody-Drug Conjugates.Biomolecules · 2026Review
- Antibody-drug conjugates in breast cancer: from mechanism to revolutionizing clinical practice.Molecular cancer · 2026Review
- De novo masking domains that gate TNF-family ligand assembly and activity.bioRxiv : the preprint server for biology · 2026Article
- Immuno-cytotoxic convergence: integrating antibody‒drug conjugates and immunofusion proteins to overcome resistance in gastrointestinal cancers.Journal of hematology & oncology · 2026Review
- Imaging-guided optimization of biodistribution and antitumor efficacy of L19-based immunocytokines.Translational oncology · 2026Article
- Targeted Therapy in Hepatobiliary Pancreatic Cancer (HPC): Advantages and Advancements of Antibody Drug Conjugates, a Type of Chemo-Biologic Hybrid Drugs.International journal of molecular sciences · 2026Review
- Clinical application and optimization strategies for antibody-drug conjugates in solid tumors.The Journal of international medical research · 2026Review
- Article
- The Recycling Collagen Receptor uPARAP Is a Unique Mediator of Stromal Drug Delivery to Carcinoma Cells.Molecular cancer therapeutics · 2026Article
- Oncofetal antigens as emerging targets in chimeric antigen receptor (CAR)-T cell-based immunotherapies: opportunities and challenges.Frontiers in cell and developmental biology · 2026Review
- Targeting splicing-derived neoantigens for precision cancer immunotherapy.Frontiers in immunology · 2026Review
- Antibody-Mediated Therapy in Gastric Cancer: Past, Present, and Future.Current issues in molecular biology · 2025Review
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- The bidirectional interplay between RNA processing and mechanotransduction.Cell reports · 2025Review
- A comparative analysis of tumor markers reveals EDA fibronectin as a promising target in high-grade serous ovarian cancer.Journal of ovarian research · 2025Article
- Exploring the mechanism of fibronectin extra domain B in the tumor microenvironment and implications for targeted immunotherapy and diagnostics (Review).Molecular medicine reports · 2025Review
Corrections and comments
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Authors and funding
24 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extra domain B splice variant of fibronectin (EDB+FN) is an extracellular matrix protein (ECM) deposited by tumor-associated fibroblasts, and is associated with tumor growth, angiogenesis, and invasion. We hypothesized that EDB+FN is a safe and abundant target for therapeutic intervention with an antibody-drug conjugate (ADC). We describe the generation, pharmacology, mechanism of action, and safety profile of an ADC specific for EDB+FN (EDB-ADC). EDB+FN is broadly expressed in the stroma of pancreatic, non-small cell lung (NSCLC), breast, ovarian, head and neck cancers, whereas restricted in normal tissues. In patient-derived xenograft (PDX), cell-line xenograft (CLX), and mouse syngeneic tumor models, EDB-ADC, conjugated to auristatin Aur0101 through site-specific technology, demonstrated potent antitumor growth inhibition. Increased phospho-histone H3, a pharmacodynamic biomarker of response, was observed in tumor cells distal to the target site of tumor ECM after EDB-ADC treatment. EDB-ADC potentiated infiltration of immune cells, including CD3+ T lymphocytes into the tumor, providing rationale for the combination of EDB-ADC with immune checkpoint therapy. EDB-ADC and anti-PD-L1 combination in a syngeneic breast tumor model led to enhanced antitumor activity with sustained tumor regressions. In nonclinical safety studies in nonhuman primates, EDB-ADC had a well-tolerated safety profile without signs of either on-target toxicity or the off-target effects typically observed with ADCs that are conjugated through conventional conjugation methods. These data highlight the potential for EDB-ADC to specifically target the tumor microenvironment, provide robust therapeutic benefits against multiple tumor types, and enhance activity antitumor in combination with checkpoint blockade.
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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.