Next-generation cell-penetrating antibodies could transform cancer treatment

A news feature on the research paper “Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition” by Rackear et al. was published in Oncotarget’s Volume 15 on November 22, 2024, titled “Advancements in cell-penetrating monoclonal antibody treatment.”

This new publication by Sai Pallavi Pradeep and Raman Bahal from the  Department of Pharmaceutical Sciences at the University of Connecticut highlights significant advancements in monoclonal antibody (mAb) therapies. The focus is on the 3E10 antibody, originally derived from autoimmune mouse studies in systemic lupus erythematosus. Unlike traditional mAbs, which struggle to reach intracellular targets, this cell-penetrating antibody targets cancer cells by addressing a major limitation of current therapies. By targeting RAD51, a key intracellular protein involved in DNA repair, the 3E10 antibody shows great promise for cancer treatment, particularly in cancers with defective DNA repair pathways.

mAbs have already changed the landscape of cancer therapy, offering treatments that are more targeted and have fewer side effects compared to chemotherapy. However, current therapies are limited since mAbs only target proteins on the surface of cancer cells. This research pushes the boundaries by demonstrating how 3E10 antibodies can penetrate cells and access their internal molecules. This unique capability expands the potential of mAb therapies and targeted cancer treatments.

Different humanized versions of the 3E10 antibody were created and carefully tested. Some versions were particularly effective at blocking RAD51, while others showed promise for carrying other therapeutic molecules like genetic material into the cancer cells. This flexibility means that 3E10 could be used to treat different cancer types and deliver various therapeutic molecules directly into tumor cells. This progress offers exciting new possibilities for treating cancer tumors that are resistant to conventional therapies.

In conclusion, the 3E10 antibody’s dual function-;targeting DNA repair pathways and delivering therapeutic molecules-;positions it as a transformative tool in cancer research and targeted cancer treatments.