Creative Biolabs provides a novel strategy that utilizes meditope technology to help clients develop customized antibody-drug conjugates (ADCs). In this methodology, the generation of meditope-enabled antibodies by site-specific carving is the core technique. Generally speaking, “Lego-like” cave sites are created on a monoclonal antibody (mAb) by switching out a few amino acid residues using antibody engineering and the resulted antibody is able to trap geometrically compliment meditopes, without the need for chemical conjugation. By adjusting and optimizing our meditope-enabled antibodies, a stable, non-covalent, yet site-specific conjugation can be achieved, resulting in the production of homogeneous ADC products with a predictable drug-to-antibody ratio (DAR).
Trapping of a meditope inside engineered cave site on Fab region. A protein was coupled with the meditope and thus “conjugated” to the antibody fragment non-covalently (PNAS, 2013).
Meditope-enabled antibodies
Meditope is a small peptide that specifically binds to a unique site located in the center of a cavity formed by the light and heavy chains of cetuximab, a chimeric, anti-epidermal growth factor receptor monoclonal antibody. Structural analysis of the three-dimensional structure of cetuximab revealed a naturally occurring “pocket” in the Fab region of the antibody that accommodates the meditope and therefore termed as “meditope-binding site”. The original study demonstrated that the binding of meditope has no significant interference with antigen binding affinity, specificity, and stability. Since this binding is specific to cetuximab, it is speculated that meditope does not bind other human mAbs. However, additional researches have shown that the meditope-binding site can be engineered into any therapeutic mAbs of interest without compromising antibody bioactivities. As a result, the meditope-enabled antibody platform is developed. The unique property of meditope-binding site can be used to directly facilitate the attachment of mAbs to a broad range of molecules through stable, non-covalent, yet site-specific interactions. Meditope-binding site represents a new avenue in the design and production of antibody-drug conjugates.
Advantages of meditope technology based conjugations:
With years of experience in antibody engineering, Creative Biolabs is committed in bringing in new technology and providing comprehensive antibody modification and conjugation strategies to help our clients with various ADC development projects, please contact us for more information and a detailed quote.
Reference:
For Research Use Only. NOT FOR CLINICAL USE.
Related Sections
One-stop ADC Development Service:Welcome! For price inquiries, please feel free to contact us through the form on the left side. We will get back to you as soon as possible.
Contact us