https://www.nature.com/articles/s41551-025-01483-9

https://sj.jst.go.jp/news/202510/n1020-02k.html

A research groupfrom the Institute for Integrated Cell-Material Sciences (iCeMS) at Kyoto University has developed a “Crunch” protein that removes unwanted but living cells in the body through phagocytosis. “Crunch” is based on protein S, a secreted factor that also binds to the Mer tyrosine kinase (MerTK) on phagocytes when during the process of engulfment of proteins into cells, phosphatidylserine is exposed on the surface of dead cells as an ‘eat-me’ signal.

They developed a synthetic protein where the phosphatidylserine-binding motif of ProS is replaced with a nanobody or single-chain variable fragment that recognized the surface proteins of targeted cells.

Green fluorescent protein nanobody-conjugated Crunch eliminated green fluorescent protein-expressing melanoma cells in transplantation mouse models. In addition, CD19⁺B cells were eliminated by anti-CD19 single-chain variable fragment-conjugated Crunch, resulting in a therapeutic effect on systemic lupus erythematosus. Both mouse and human versions of Crunch were effective, suggesting that this synthetic ligand is a promising tool for the elimination of targeted cells.