ArticleCell reports. Medicine2021
A GPC2 antibody-drug conjugate is efficacious against neuroblastoma and small-cell lung cancer via binding a conformational epitope.
Article in Cell reports. Medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 33 citations in OpenAlex.
- Paediatric Therapeutic Development Workshop on rhabdomyosarcoma.British journal of cancer · 2026Review
- mRNA vaccination using peptide nanoparticles triggers a strong immune response against endogenous GPC2 in a murine neuroblastoma model.Molecular therapy. Oncology · 2026Article
- Article
- Established and Emerging Therapies for High-Risk Neuroblastoma.Paediatric drugs · 2026Review
- Review
- Scratching the surface of targeting GPC2 on pediatric CNS tumors.Molecular therapy. Oncology · 2025Article
- D3-GPC2-Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Advancing liver cancer diagnosis and treatment with multi-omics approaches: a systematic review.Discover oncology · 2025Review
- Structure and Function of the Extracellular Matrix in Normal and Pathological Conditions: Looking at the Bicuspid Aortic Valve.International journal of molecular sciences · 2025Review
- Reprogramming the neuroblastoma tumor immune microenvironment to enhance GPC2 CAR T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Heparan Sulfate Proteoglycans as Potential Markers for In Vitro Human Neural Lineage Specification.Cells · 2025Article
- Lineage dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and -independent immunotherapeutic targets.Neuro-oncology · 2025Article
- Structural Features of Glypicans and their Impact on Wnt Signaling in Cancer.Proteoglycan research · 2025Article
- Antibody conjugates in neuroblastoma: a step forward in precision medicine.Frontiers in oncology · 2025Review
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
- CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma.Nature communications · 2024Article
- Targeting GPC2 on Intraocular and CNS Metastatic Retinoblastomas with Local and Systemic Delivery of CAR T Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- GPC2 promotes prostate cancer progression via MDK-mediated activation of PI3K/AKT signaling pathway.Functional & integrative genomics · 2024Article
- UCHL1 is a potential molecular indicator and therapeutic target for neuroendocrine carcinomas.Cell reports. Medicine · 2024Article
- The current status and future of ADC therapy for small cell Lung Cancer: a promising approach.Journal of translational medicine · 2023Article
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
Glypican 2 (GPC2) is a MYCN-regulated, differentially expressed cell-surface oncoprotein and target for immune-based therapies in neuroblastoma. Here, we build on GPC2's immunotherapeutic attributes by finding that it is also a highly expressed, MYCN-driven oncoprotein on small-cell lung cancers (SCLCs), with significantly enriched expression in both the SCLC and neuroblastoma stem cell compartment.By solving the crystal structure of the D3-GPC2-Fab/GPC2 complex at 3.3 Å resolution, we further illustrate that the GPC2-directed antibody-drug conjugate (ADC; D3-GPC2-PBD), that links a human GPC2 antibody (D3) to DNA-damaging pyrrolobenzodiazepine (PBD) dimers, binds a tumor-specific, conformation-dependent epitope of the core GPC2 extracellular domain. We then show that this ADC induces durable neuroblastoma and SCLC tumor regression via induction of DNA damage, apoptosis, and bystander cell killing, notably with no signs of ADC-induced
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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.