ArticleThe Journal of clinical investigation2022
Targeting a proteolytic neoepitope on CUB domain containing protein 1 (CDCP1) for RAS-driven cancers.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Proteomic characterization of intrahepatic cholangiocarcinoma identifies risk-stratifying subgroups and EIF4A1 as a therapeutic target.Nature communications · 2026Article
- High CDCP1 Expression Reflects Immune and Stromal Remodeling and Oncogenic Signaling in Pancreatic Ductal Adenocarcinoma.World journal of oncology · 2026Article
- CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer.British journal of cancer · 2025Article
- Hijacking Extracellular Targeted Protein Degrader-Drug Conjugates for Enhanced Drug Delivery.Journal of the American Chemical Society · 2025Article
- CDCP1-targeting ADC outperforms standard therapies in Ras-mutant pancreatic cancer.Molecular therapy. Oncology · 2025Article
- Low-density lipoprotein receptor-targeting chimeras for membrane protein degradation and enhanced drug delivery.bioRxiv : the preprint server for biology · 2025Article
- Hypoxia Induces Extensive Protein and Proteolytic Remodeling of the Cell Surface in Pancreatic Adenocarcinoma (PDAC) Cell Lines.Journal of proteome research · 2025Article
- Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome.Chemical reviews · 2025Review
- Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance.Pharmaceutics · 2024Review
- Pre-diagnostic plasma inflammatory proteins and risk of hepatocellular carcinoma in three population-based cohort studies from the United States and the United Kingdom.International journal of cancer · 2024Article
- Targeting CDCP1 boost CD8+ T cells-mediated cytotoxicity in cervical cancer via the JAK/STAT signaling pathway.Journal for immunotherapy of cancer · 2024Article
- Multiscale photocatalytic proximity labeling reveals cell surface neighbors on and between cells.Science (New York, N.Y.) · 2024Article
- A general approach for selection of epitope-directed binders to proteins.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Identification and multicentric validation of soluble CDCP1 as a robust serological biomarker for risk stratification of NASH in obese Chinese.Cell reports. Medicine · 2023Article
- Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role ofCirculation research · 2023Article
- Theranostic Targeting of CUB Domain-Containing Protein 1 (CDCP1) in Multiple Subtypes of Bladder Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Mechanistic insights into CDCP1 clustering on non-small-cell lung cancer membranes revealed by super-resolution fluorescent imaging.iScience · 2023Article
- CDCP1 (CUB domain containing protein 1) is a potential urine-based biomarker in the diagnosis of low-grade urothelial carcinoma.PloS one · 2023Article
- Direct Identification of Proteolytic Cleavages on Living Cells Using a Glycan-Tethered Peptide Ligase.ACS central science · 2022Article
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14 authors at 4 institutions in 2 countries.
Funding
Abstract
Extracellular proteolysis is frequently dysregulated in disease and can generate proteoforms with unique neoepitopes not found in healthy tissue. Here, we demonstrate that Abs that selectively recognize a proteolytic neoepitope on CUB domain containing protein 1 (CDCP1) could enable more effective and safer treatments for solid tumors. CDCP1 is highly overexpressed in RAS-driven cancers, and its ectodomain is cleaved by extracellular proteases. Biochemical, biophysical, and structural characterization revealed that the 2 cleaved fragments of CDCP1 remain tightly associated with minimal proteolysis-induced conformational change. Using differential phage display, we generated recombinant Abs that are exquisitely selective to cleaved CDCP1 with no detectable binding to the uncleaved form. These Abs potently targeted cleaved CDCP1-expressing cancer cells as an Ab-drug conjugate, an Ab-radionuclide conjugate, and a bispecific T cell engager. In a syngeneic pancreatic tumor model, these cleaved-specific Abs showed tumor-specific localization and antitumor activity with superior safety profiles compared with a pan-CDCP1 approach. Targeting proteolytic neoepitopes could provide an orthogonal "AND" gate for improving the therapeutic index.
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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 Socratic graph.