AsianScientist (Nov. 25, 2025) – The human body has its own cleanup crew—immune cells called phagocytes that scout out and engulf debris or dead cells in our tissues. In a study published in Nature Bioengineering, scientists at Kyoto University in Japan are harnessing this natural cell disposal machinery to clear out troublemaking cells like those involved in cancer or autoimmune diseases.
When cells are ready to be removed, they display phosphatidylserine, a fat-like molecule on their surface that tags them for clearance. A plasma protein in the blood named Protein S then binds to this tag on dying cells while simultaneously attaching to a receptor on phagocytes, bringing the two together and triggering engulfment, or more specifically ‘phagocytosis’.
“What we’ve done is take that natural cleaning system and reprogram it to target living cells that shouldn’t be there,” said the study’s first author, Yuki Yamato who was a doctoral student at the Graduate School of Biostudies at Kyoto University.
“We built Crunch by modifying Protein S, which normally helps phagocytes recognize dead cells. But instead of binding to dead cells, we gave Crunch the ability to recognize specific living cells we want to remove, like cancer cells or overactive immune cells in autoimmune diseases,” Yamato explained.
The researchers engineered Crunch by replacing its typical binding site for dead-cell lipids with a customizable binding component for the unique surface markers on targeted cells.
“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 Jun Suzuki, a professor at Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS) who led the study.
“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,” said Suzuki.
This is the first time the body’s innate cleanup system has been repurposed as a therapeutic tool. Crunch’s success in animal disease models suggests a new frontier in precision therapeutics, one that could overcome the challenges of current treatment options that reprogram the immune system.
For instance, CAR-T cell therapy requires collecting, modifying and reinfusing a patient’s immune cells to attack cancer. As a protein-based treatment, Crunch could instead be administered through an injection.
“We think this could become a new kind of therapy that can be adapted to many conditions. We can also adopt the targeting sensors from antibodies and CAR-T. It’s the ecosystem for the various therapeutic tools” said Suzuki.
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Source: Kyoto University ; Image: Shutterstock
This article can be found at Phagocytic clearance of targeted cells with a synthetic ligand.
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