Super-strong antibodies developed for cancer treatment

Scientists at the University of Southampton say they have engineered a new type of super-strong antibody which could be used to boost the immune systems of patients fighting cancer, with the results of their research published in the journal Nature Communications.

The scientists altered the shape and flexibility of the tiny proteins, which are naturally produced by white blood cells to protect the body from bacteria and viruses. They discovered that their antibody prototype, which was more rigid, was able to trigger a stronger response from the immune system compared to those made by our bodies.

“The concept of using immuno-stimulation for cancer treatment is very exciting,” said Professor Mark Cragg, from Southampton’s Centre for Cancer Immunology.

“Our study confirms that making even subtle increases in the rigidity of antibodies significantly stimulates immune activity, creating a powerful immune response against the disease.

“This approach works for multiple antibodies targeting different immune receptors.

“The ability to engineer these rigid antibodies could help develop more potent drugs that can stimulate the immune system to target cancer or other diseases.”

The Y-shaped antibodies fight infections by targeting and then binding onto molecules on the surface of bacteria and viruses, or even cancerous cells. They can also be engineered to attach to receptors on immune cells to activate our body’s immune defences. But not all antibodies do this effectively, according to Southampton PhD student and study co-author Isabel Elliott.

“The shape and flexibility of antibodies is crucial for how well they can activate immune cells — and we found more rigid antibodies seem to be better at this,” Elliott said.

“The reason for this is likely because these rigid antibodies can hold molecules on the immune cells closer together, which triggers a stronger activation signal.

“Floppier antibodies are less likely to do this effectively.”

The two arms of an antibody, which give it its Y shape, are linked by a series of bridges, named disulfide bonds. The Southampton scientists managed to add extra bridges between the microscopic arms of the antibody and tested it against standard variants.

“We used a supercomputer to visualise the structure of the antibody in atomic detail, allowing us to position extra disulfide bonds in the modified antibody,” said Southampton’s Dr Ivo Tews.

“The results showed that the experiment worked and that the new, more rigid antibodies were more effective at activating immune cells.

“This idea of controlling antibody activity by making them more rigid seems to apply to many other similar molecules on immune cells.”

The study was funded by Cancer Research UK, whose Executive Director of Research and Innovation, Dr Iain Foulkes, said: “Refining our understanding of how to enable our immune systems to fight cancer is a complex but fundamental step in helping cancer patients to have the best chance of a good outcome when receiving immunotherapy treatment.”

Foulkes added, “Using the latest technologies to engineer this type of super-strong antibody that could trigger a promising immune response will empower us to continue pioneering new ways to outsmart cancer.”

Image credit: iStock.com/bodym