ArticleProceedings of the National Academy of Sciences of the United States of America2017
Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 144 citations in OpenAlex.
- Development of novel GPC2-directed radiotheranostics and CAR T cell therapy for neuroblastoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Antibody format matters: A comparative analysis of VHH and scFv domains reveals superior in vivo CAR T cell function with VHH domains.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- A Festschrift Celebrating Dr. Dimiter Stanchev Dimitrov: Antibodies, Innovation, and Impact on Infectious Disease and Cancer Research.Antibodies (Basel, Switzerland) · 2026Article
- Allogeneic CRISPR-Engineered CAR-T Cells Drive Potent Antitumor Activity in Solid Tumors.bioRxiv : the preprint server for biology · 2026Article
- Article
- GPC2-CAR T cells have potent preclinical activity against orthotopic medulloblastoma xenografts.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
- Application of nanobody‑based CAR‑T in tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Antibody-gamma/delta T cell receptors targeting GPC2 regress neuroblastoma with low antigen density.Cell reports. Medicine · 2025Article
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 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
- Defining the extracellular matrix for targeted immunotherapy in adult and pediatric brain cancer.NPJ precision oncology · 2025Article
- GRP78 Nanobody-Directed Immunotoxin Activates Innate Immunity Through STING Pathway to Synergize Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Structural Features of Glypicans and their Impact on Wnt Signaling in Cancer.Proteoglycan research · 2025Article
- Nanobody-enhanced chimeric antigen receptor T-cell therapy: overcoming barriers in solid tumors with VHH and VNAR-based constructs.Biomarker research · 2025Review
- Antibody conjugates in neuroblastoma: a step forward in precision medicine.Frontiers in oncology · 2025Review
- A new treatment for canine B-cell lymphoma based on a recombinant single-domain antibody immunotoxin derived fromFrontiers in veterinary science · 2025Article
- CAR T-cells for pediatric solid tumors: where to go from here?Cancer metastasis reviews · 2024Review
- CAR T-cell-mediated delivery of bispecific innate immune cell engagers for neuroblastoma.Nature communications · 2024Article
- Cancer therapy with antibodies.Nature reviews. Cancer · 2024Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Neuroblastoma is a childhood cancer that is fatal in almost half of patients despite intense multimodality treatment. This cancer is derived from neuroendocrine tissue located in the sympathetic nervous system. Glypican-2 (GPC2) is a cell surface heparan sulfate proteoglycan that is important for neuronal cell adhesion and neurite outgrowth. In this study, we find that GPC2 protein is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival compared with patients with low GPC2 expression. We demonstrate that silencing of GPC2 by CRISPR-Cas9 or siRNA results in the inhibition of neuroblastoma tumor cell growth. GPC2 silencing inactivates Wnt/β-catenin signaling and reduces the expression of the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. We have isolated human single-domain antibodies specific for GPC2 by phage display technology and found that the single-domain antibodies can inhibit active β-catenin signaling by disrupting the interaction of GPC2 and Wnt3a. To explore GPC2 as a potential target in neuroblastoma, we have developed two forms of antibody therapeutics, immunotoxins and chimeric antigen receptor (CAR) T cells. Immunotoxin treatment was demonstrated to inhibit neuroblastoma growth in mice. CAR T cells targeting GPC2 eliminated tumors in a disseminated neuroblastoma mouse model where tumor metastasis had spread to multiple clinically relevant sites, including spine, skull, legs, and pelvis. This study suggests GPC2 as a promising therapeutic target in neuroblastoma.
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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.