Protein-based therapy helps the body remove harmful cells

Scientists at Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS) have created a protein-based therapeutic tool that could change the way we treat diseases caused by harmful or unnecessary cells. Described in the journal Nature Biomedical Engineering, the tool involves a synthetic protein called Crunch — short for Connector for Removal of Unwanted Cell Habitat — which uses the body’s natural waste removal system to clear out specific target cells, offering hope for treating diseases where harmful cells cause damage.

Every day, billions of our body’s cells naturally die as part of normal processes, before being cleaned up by immune cells called phagocytes. Phagocytes act like microscopic vacuum cleaners, spotting dying cells by detecting an ‘eat me’ signal on their surface. Once they recognise that signal, they surround and digest the dead cells.

“What we’ve done is take that natural cleaning system and reprogram it to target living cells that shouldn’t be there,” said Yuki Yamato, first author on the new study. “We built Crunch by modifying a protein called Protein S, which normally helps phagocytes recognise dead cells. But instead of binding to dead cells, we gave Crunch the ability to recognise specific living cells we want to remove, like cancer cells or overactive immune cells in autoimmune diseases.”

To do this, the researchers replaced the part of Protein S that detects dying cells with a kind of sensor that can recognise unique surface proteins found only on the unwanted cells. These sensors can be designed in an order-made way to target almost any type of cell. Once Crunch binds to its chosen target, it connects that cell to the phagocytes, which then engulf and break it down.

Crunch works like a high-precision delivery tag. It doesn’t kill the cells directly; instead, it labels them in a way that tricks the immune system into thinking they are ready for removal. This makes the body itself clear them out, using processes it already relies on every day.

“In mice, we used Crunch to get rid of cancer cells that were made to express specific cell surface protein, so we could track them,” said study leader Professor Jun Suzuki. “We also used it to eliminate certain immune cells in a model of lupus, a disease where the immune system attacks healthy tissue. In both cases, the harmful cells were successfully cleared, and signs of disease were reduced.”

The new tool could prove to be helpful for treating cancer, autoimmune diseases, and other diseases where current treatments such as CAR-T cell therapy and antibody-based drugs have certain limitations. In the case of CAR-T, blood cells are collected from the patient, modified in the lab and then put back. Crunch, on the other hand, is a protein-based therapy that could potentially be delivered through a simple injection.

Furthermore, because Crunch’s targeting sensor can be modified depending on the disease, it acts like a customisable platform. The team is now working to make the tool safer, easier to produce, and more effective in real-life settings.

“We think this could become a new kind of therapy that can be adapted to many conditions,” Suzuki said. “We can also adopt the targeting sensors from antibodies and CAR-T. It’s the ecosystem for the various therapeutic tools.”

Image caption: Crunch helps immune cells recognise and remove harmful cells by connecting them directly to specific targets, guiding the body’s natural clean-up process. Image credit: Mindy Takamiya/Kyoto University iCeMS.