Antibodies are blood proteins with highly specialized functions: to recognize and eliminate bacteria, viruses, and other foreign substances in the body. Inspired by the exquisite specificity of these molecules, drug developers have been turning them into therapies for a range of diseases, including cancer.
The first approved monoclonal antibody to treat blood cancers (a drug called rituximab) paved the way for a long line of similar biologics to enter the clinic. The problem, however, is that these therapies don't work for all patients. Additionally, in the patients who respond, the cancer-killing effects of antibody treatments wane over time as tumors develop resistance.
Due to these limitations, researchers have been seeking ways of enhancing cancer biologics. Recent work by scientists at the University of Southampton, in collaboration with biopharma partner UCB, has seen a breakthrough in the field—engineered antibodies with a unique 2-in-1 feature for combating cancer.
The new platform combines distinctive properties of two antibody classes, IgM and IgG, to improve the therapeutic effectiveness of the resulting hybrid antibody. A modified IgM' tailpiece' is fused to the C-terminus of IgG. This addition of the C757S-tailpiece—a small, 18 amino-acid peptide—activates the complement pathway to enhance target cell killing while limiting adverse side effects in patients. The innovators of the method see this as a plug-and-play tool where the tailpiece can be engineered onto existing antibodies, turning them into what they call 'bio-betters'.
Lead researcher Mark Cragg from the University of Southampton said, "Antibody engineering is a fascinating area and allows us to take advantage of the fantastic molecules that nature has evolved to combat infection and improve on them for our therapeutic purposes."