Novel antibodies show promise for tumor targeting and RAD51 inhibition

A new research paper was published in Oncotarget's Volume 15 on October 1, 2024, entitled, "Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition."

As highlighted in the abstract, monoclonal antibody therapies for cancer have shown extraordinary clinical success in recent years. However, these strategies are primarily limited to targeting specific cell surface antigens, despite many disease targets being located intracellularly.

In their paper, researchers Madison Rackear, Elias Quijano, Zaira Ianniello, Daniel A. Colón-Ríos, Adam Krysztofiak, Rashed Abdullah, Yanfeng Liu, Faye A. Rogers, Dale L. Ludwig, Rohini Dwivedi, Franziska Bleichert, and Peter M. Glazer from the Departments of Therapeutic Radiology and Genetics at Yale University School of Medicine, Gennao Bio, and the Department of Molecular Biophysics and Biochemistry at Yale University report on the humanization of the full-length, nucleic acid-binding monoclonal lupus-derived autoantibody 3E10, which exhibits a novel mechanism for cell penetration and tumor-specific targeting.

The authors compare humanized variants of 3E10 and demonstrate that cell uptake relies on the nucleoside transporter ENT2. They also find that faster cell uptake and superior in vivo tumor targeting are associated with higher affinity nucleic acid binding.

"We show that one human variant retains the ability of the parental 3E10 to bind RAD51, serving as a synthetically lethal inhibitor of homology-directed repair in vitro."