ArticleScience signaling2025
A lupus-derived autoantibody that binds to intracellular RNA activates cGAS-mediated tumor immunity and can deliver RNA into cells.
Article in Science signaling, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Myositis-specific autoantibodies recognising Mi2 also target the AIRE protein at a shared PHD zinc finger.Annals of the rheumatic diseases · 2026Article
- Antimitochondrial antibodies in systemic sclerosis target enteric neurons and are associated with GI dysmotility.Annals of the rheumatic diseases · 2025Article
- Protein Functional Effector (pfe) Noncoding RNAS Are Identical to Fragments from Various Noncoding RNAs.International journal of molecular sciences · 2025Article
- Characterization of TrkB autoantibodies reveals an agonist binding region in breast cancer.American journal of cancer research · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Nucleic acid-mediated signaling triggers an immune response that is believed to be central to the pathophysiology of autoimmunity in systemic lupus erythematosus (SLE). Here, we found that a cell-penetrating, SLE-associated antiguanosine autoantibody may present therapeutic opportunities for cancer treatment. The autoantibody entered cells through a nucleoside salvage-linked pathway of membrane transit that avoids endosomes and lysosomes and bound to endogenous RNA in live cells. In orthotopic models of glioblastoma, the antibody localized to areas adjacent to necrotic tumor cells and promoted animal survival in a manner that depended on T cells. Mechanistic studies revealed that antibody binding to nucleic acids activated the cytoplasmic pattern recognition receptor cyclic GMP-AMP synthase (cGAS), thereby stimulating immune signaling and cGAS-dependent cytotoxicity. Moreover, the autoantibody could carry and deliver functional RNA into tumor, brain, and muscle tissues in live mice when administered locally. The findings establish a collaborative autoantibody-nucleic acid interaction that is translatable to strategies for nonviral gene delivery and immunotherapy.
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Registered trials
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