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Cell-penetrating, DNA-targeting systemic lupus erythematosus (SLE) autoantibody 3E10 for sensitizing cancers to DNA-damaging agents

In vitro and mouse studies suggest lupus autoantibodies targeting DNA could help sensitize tumors to DNA-damaging agents. In human breast cancer and glioma cells and in a mouse xenograft model of human glioma, the DNA-targeting SLE autoantibody 3E10 plus ionizing radiation or doxorubicin increased cell death and tumor suppression compared with radiation or doxorubicin alone. In DNA binding assays, 3E10 bound single-stranded DNA and inhibited DNA repair. In cancer cells with breast cancer 2 early onset (BRCA2) mutations that impair DNA-damage responses, 3E10 alone showed cytotoxicity. Next steps include identifying tumor types most sensitive to the autoantibody.

SciBX 5(43); doi:10.1038/scibx.2012.1148
Published online Nov. 1, 2012

Patent application filed covering use of cell-penetrating autoantibodies to treat cancer; available for licensing

Hansen, J.E. et al. Sci. Transl. Med.; published online Oct. 24, 2012;
Contact: Peter M. Glazer, Yale School of Medicine, New Haven, Conn.