Orum team describes cell-permeable, Ras-targeting mAb

In a paper published in Nature Communications, researchers showed that a cell-permeable antibody targeting Ras slowed growth of cancer cell lines with minimal toxicity in cells without aberrant Ras activity, suggesting its therapeutic potential. The group included scientists from Orum Therapeutics Inc. (Daejeon, South Korea), who used the company's cell-penetrating technology platform.

Orum’s platform is designed to help biologics escape intracellular degradation, enabling them to inhibit cytosolic proteins such as Ras that are hard to target with small molecules. The group uses an engineered, light chain variable domain (VL) that replaces both VLs in a standard IgG antibody, allowing it to interact with heparan sulfate proteoglycans (HSPGs) and begin receptor-mediated endocytosis. Once inside the acidic environment of the endosome, the domain undergoes a conformational change that creates pores in the endosomal membrane through which the antibody can escape (see BioCentury Innovations, Jan. 4)...