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. 2020 Jun 24;11:3196. doi: 10.1038/s41467-020-16838-w

Fig. 1. Mode of action of protease-activated FOLR1-TCB.

Fig. 1

On the left panel, the anti-CD3 Fab is blocked by an anti-idiotypic anti-CD3 scFv and thus cannot activate T cells against FOLR1-expressing cells. On the right panel, the linker containing a tumor-specific protease site has been cleaved and the anti-CD3 moiety is active leading to lysis of FOLR1-expressing cells. The figure shows an idealized representation of the Prot-FOLR1-TCB before (left) and after (right) cleavage at the matriptase cleavage site (cyan). The model is based on the full-length IgG crystal structure with PDB ID 1hzh. The protected anti-CD3ε Fab was modeled based on the crystal structure of an idiotype-anti-idiotype Fab complex structure with PDB ID 1iai. The catalytic domain of matriptase (crystal structure with PDB ID 1eax) is shown for reference (gray). Visualized with Biovia Discovery Studio 17R2 and arranged with GIMP. TME tumor microenvironment.