• Monoclonal antibodies (mAbs)
have exceptional specificity and favorable pharmacology therefore, substantial
efforts have been made to functionalize them, either with potent cytotoxins,
biologics, radionuclides, or fluorescent groups for therapeutic benefit and/or
use as theranostic
agents.
• To exploit the discovered meditope–Fab
interaction as an alternative means to efficiently functionalize mAbs,
inventors used insights from the structure to enhance the affinity and lifetime
of the interaction by four orders of magnitude.
• To further extend the lifetime of the
complex, inventors created a mechanical bond by incorporating an azide on
the meditope,
threading the azide through the Fab, and using click
chemistry to add a steric group. The mechanically interlocked, meditope–Fab
complex retains antigen specificity and is capable of imaging tumors in mice.
• These results indicate it is possible to
“snap” functionality onto mAbs, opening the possibility of rapidly
creating unique combinations of mAbs with an array of cytotoxins, biologics,
and imaging agents.
