ArticleJCI insight2021
ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Autoantibody internalization in myositis skeletal muscle: Emerging evidence, mechanistic insights, and therapeutic relevance.Autoimmunity reviews · 2026Review
- Oncolytic bacteria therapy for malignant glioma.Frontiers in immunology · 2026Review
- New therapeutic strategies for Lafora disease: Evaluation of the safety, efficacy, pharmacokinetics and metabolomic profile of intravenous VAL-1221 treatment.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Cell-penetrating antibody enhances nuclear delivery of triplex-forming oligonucleotides targeting HER2-positive cancers.Molecular therapy. Nucleic acids · 2025Article
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- Harnessing ExDNA for precision exatecan delivery in cancer: a novel antibody-drug conjugate approach.Molecular cancer · 2025Article
- A lupus-derived autoantibody that binds to intracellular RNA activates cGAS-mediated tumor immunity and can deliver RNA into cells.Science signaling · 2025Article
- Advancements in cell-penetrating monoclonal antibody treatment.Oncotarget · 2024Article
- VAL-1221 for the treatment of patients with Lafora disease: study protocol for a single-arm, open-label clinical trial.BMJ open · 2024Article
- Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition.Oncotarget · 2024Article
- Cathepsin B Nuclear Flux in a DNA-Guided "Antinuclear Missile" Cancer Therapy.ACS central science · 2024Article
- An Emerging Role for Anti-DNA Antibodies in Systemic Lupus Erythematosus.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
The blood-brain barrier (BBB) prevents antibodies from penetrating the CNS and limits conventional antibody-based approaches to brain tumors. We now show that ENT2, a transporter that regulates nucleoside flux at the BBB, may offer an unexpected path to circumventing this barrier to allow targeting of brain tumors with an anti-DNA autoantibody. Deoxymab-1 (DX1) is a DNA-damaging autoantibody that localizes to tumors and is synthetically lethal to cancer cells with defects in the DNA damage response. We found that DX1 penetrated brain endothelial cells and crossed the BBB, and mechanistic studies identify ENT2 as the key transporter. In efficacy studies, DX1 crosses the BBB to suppress orthotopic glioblastoma and breast cancer brain metastases. ENT2-linked transport of autoantibodies across the BBB has potential to be exploited in brain tumor immunotherapy, and its discovery raises hypotheses on actionable mechanisms of CNS penetration by neurotoxic autoantibodies in CNS lupus.
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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.