ArticleJournal for immunotherapy of cancer2023
A highly selective humanized DDR1 mAb reverses immune exclusion by disrupting collagen fiber alignment in breast cancer.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026Review
- Collagen-Binding IL-15 Immunocytokine Armed Oncolytic Adenovirus Establishes a Self-Reinforcing Immunostimulatory Milieu to Potentiate Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Supermeres Containing the Discoidin Domain Receptor 1 Extracellular Domain Promote Collagen Alignment and Immune Exclusion in Microsatellite-Stable Colorectal Cancer.Cancer research communications · 2026Article
- Single nucleus RNA profiling reveals potential therapeutic vulnerabilities in sinonasal carcinomas.NPJ precision oncology · 2026Article
- Targeting the Barriers Driving Immune Exclusion.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Bioinformatic pipeline to identify potential therapeutic targets with subsequent isolation and characterization of novel human anti- DDR1 antibodies.Scientific reports · 2026Article
- Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Decoding collagen cues: the interplay of integrins and discoidin domain receptors in health and disease.Journal of biomedical science · 2026Review
- Targeting Tumor-Associated Macrophages to Reshape the Immuno-Mechanical Landscape: Molecular Mechanisms and Therapeutic Strategies.International journal of biological sciences · 2026Review
- The Diagnostic Role and Potential Pharmacological Value of DDR1 in Pan-Cancer.Current topics in medicinal chemistry · 2026Article
- An Overview of Emerging Trends in Targeted Therapy of Triple-Negative Breast Cancer.International journal of breast cancer · 2026Review
- Breast cancer pathogenesis, diagnosis and treatment: a comprehensive review.Frontiers in oncology · 2026Review
- Collagen dynamics in the breast cancer tumor microenvironment and therapeutic perspectives.Discover oncology · 2025Review
- Recent progress in immune evasion mechanisms of triple-negative breast cancer.Journal of translational medicine · 2025Review
- Targeted DDR1 Treatment Strategy Enhances PD-1 Immunotherapy Efficacy against Gastric Cancer.Journal of medicinal chemistry · 2025Article
- DDR1 drives cervical cancer progression and immune evasion: a bioinformatics analysis with experimental verification.BMC cancer · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Inhibition of DDR1 potentiates carbon ion radiotherapy by promoting ferroptosis and immunogenic death in head and neck squamous cell carcinoma.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundImmune exclusion (IE) where tumors deter the infiltration of immune cells into the tumor microenvironment has emerged as a key mechanism underlying immunotherapy resistance. We recently reported a novel role of discoidin domain-containing receptor 1 (DDR1) in promoting IE in breast cancer and validated its critical role in IE using neutralizing rabbit monoclonal antibodies (mAbs) in multiple mouse tumor models.
methodsTo develop a DDR1-targeting mAb as a potential cancer therapeutic, we humanized mAb9 with a complementarity-determining region grafting strategy. The humanized antibody named PRTH-101 is currently being tested in a Phase 1 clinical trial. We determined the binding epitope of PRTH-101 from the crystal structure of the complex between DDR1 extracellular domain (ECD) and the PRTH-101 Fab fragment with 3.15 Å resolution. We revealed the underlying mechanisms of action of PRTH-101 using both cell culture assays and
resultsPRTH-101 has subnanomolar affinity to DDR1 and potent antitumor efficacy similar to the parental rabbit mAb after humanization. Structural information illustrated that PRTH-101 interacts with the discoidin (DS)-like domain, but not the collagen-binding DS domain of DDR1. Mechanistically, we showed that PRTH-101 inhibited DDR1 phosphorylation, decreased collagen-mediated cell attachment, and significantly blocked DDR1 shedding from the cell surface. Treatment of tumor-bearing mice with PRTH-101
conclusionsThis study not only paves a pathway for the development of PRTH-101 as a cancer therapeutic, but also sheds light on a new therapeutic strategy to modulate collagen alignment in the tumor ECM for enhancing antitumor immunity.
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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.