Anti-DNA autoantibodies reveal toxicity to tumor cell lines

Antibody-Dependent Cell-Mediated Cytotoxicity- and Complement-Dependent Cytotoxicity-Independent Bactericidal Activity of an IgG against Pseudomonas aeruginosa O6ad

“…Some cytotoxic Abs to microorganisms or mammalian cells trigger target cell death by DNA or protein hydrolysis (53)(54)(55)(56)(57)(58)(59) or by production of toxic oxidative molecules (i.e., H 2 O 2 , O 3 , and hydroxide radials) via catalyzing water oxidation reactions (13)(14)(15). Our data exclude the possibility that the anti-O6ad Abs exert their bactericidal action through DNase (Supplemental Fig.…”

A nucleic acid-hydrolyzing antibody penetrates into cells via caveolae-mediated endocytosis, localizes in the cytosol and exhibits cytotoxicity

“…7D) demonstrated that 3D8 scFv induced apoptotic cell death. Previous reports have shown that cell-penetrating anti-DNA Abs with DNA-hydrolyzing activity also showed cytotoxicity, triggering apoptosis in various cancer cells [3,6]: anti-DNA Abs were internalized and accumulated in the nucleus, leading the authors to postulate that apoptotic cell death was triggered by damage to nuclear DNA [3,6]. Unlike the above cellpenetrating anti-DNA Abs, however, the final destination of 3D8 scFv up to 48 h was the cytosol without accumulation in the nucleus (Fig.…”

“…Unlike CPPs which do not generally exhibit cytotoxicity, cellpenetrating anti-DNA Abs with DNA-hydrolyzing activity induced apoptotic cell death [3,4]. Even though their cell-penetrating capacity has not yet been investigated in detail, some polyclonal anti-DNA Abs have shown that their DNA-hydrolyzing activity is correlated with cytotoxicity to tumor cells [5,6].…”

Cell-penetrating autoantibody induces caspase-mediated apoptosis through catalytic hydrolysis of DNA

“…21 Penetration of autoantibodies into living cells and nuclear localization supports the possible interaction between the autoantibodies and nuclear DNA as well as the role of the autoantibody in the pathogenesis and tissue damage of autoimmune diseases. 3 …”

“…1 Some anti-DNA autoantibodies have been known to have nuclease or protease activity as well as cytotoxicity in vitro. 2,3 Antibodies (Abs) with nuclease or protease activities, known as catalytic Abs, are found in autoimmune-prone mice more frequently than in normal mice, 4,5 suggesting that catalytic activity participates in the unique function and pathogenesis of autoantibodies. Catalytic Abs have been generated by in vitro immunization in autoimmune-prone and normal mice using transition state analogs as haptens.…”