Publications by authors named "Leah Goodstein"
The high specificity and favorable pharmacological properties of monoclonal antibodies (mAbs) have prompted significant interest in re-engineering this class of molecules to add novel functionalities for enhanced therapeutic and diagnostic potential. Here, we used the high affinity, meditope-Fab interaction to template and drive the rapid, efficient, and stable site-specific formation of a disulfide bond. We demonstrate that this template-catalyzed strategy provides a consistent and reproducible means to conjugate fluorescent dyes, cytotoxins, or "click" chemistry handles to meditope-enabled mAbs (memAbs) and memFabs.
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- Monoclonal antibodies (mAbs) are highly specific and effective, leading to efforts to enhance their function with various therapeutic agents for better treatment outcomes and diagnostic purposes.
- Researchers discovered a new interaction called meditope-Fab that significantly improves the binding affinity and stability of mAbs, increasing their effectiveness.
- By creating a mechanical bond using click chemistry, these enhanced mAbs can retain their specific targeting ability while also being used for tumor imaging in mice, suggesting potential for rapid development of new mAb combinations for therapy and diagnostics.
We have previously identified a cyclic peptide called meditope which binds to the central cavity of the Fab portion of cetuximab and shown that this peptide binding site can be grafted, or 'meditope-enabled', onto trastuzumab. This peptide has been shown to act as a hitch for the non-covalent attachment of imaging agents to meditope-enabled antibodies. Herein, we explore the process of grafting this peptide binding site onto M5A, an anti-CEA antibody in clinical trials for cancer diagnostics.
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