Thursday, October 31, 2013
Meditope-enabled mAbs. As
reported by Donaldson et al., the Fab framework of the chimeric anti-epidermal growth factor receptor
(EGFR) mAb Erbitux cetuximab
contains a unique peptide-binding site that is distinct from the antibody's
antigen-binding sites. This site is located in the center of a cavity formed by
the mAb's light and heavy chains and can bind to engineered peptides called meditopes
without interfering with antigen binding.
The meditope-binding site can be engineered into other mAbs, such as the anti-HER2 (EGFR2; ErbB2; neu) mAb Herceptin trastuzumab.
mAbs can be conjugated to a broad range of molecules and thus represent a new
avenue in antibody-drug conjugates. A meditope-enabled mAb can be used to
target many otherwise nonspecific agents without the need to make additional
modifications to the mAb itself.
Potential applications include using meditope-enabled mAbs plus
meditope-peptide conjugates to deliver imaging agents [green stars] or therapeutic
payloads [red stars] to target cells.