12:00 AM
Oct 31, 2013
 |  BC Innovations  |  Cover Story

Building meditope-enabled mAbs

Linker technologies for generating antibody-drug conjugates typically require a labor-intensive process of reengineering the antibody for every application. Researchers at the Beckman Research Institute at City of Hope have published proof-of-concept data on a platform to generate mAb conjugates with other molecules of interest that eliminates the need to reengineer the antibody for each conjugate.1

Institute spinout Meditope Biosciences Inc. is commercializing the technology, which involves building a site into mAbs that can bind to peptides called meditopes that serve as linkers to various payloads. The startup raised $3.6 million in a series A round in July and is seeking industry partnerships.

Antibody-drug conjugate (ADC) linkers can disrupt a mAb's native properties in an undesirable manner-for example, by decreasing antigen-binding affinity, specificity and stability or increasing immunogenicity.2

Thus, researchers need to reassess and likely reoptimize the properties of a mAb each time they reengineer it to carry a different molecule. Doing so is labor intensive and can become cost prohibitive when generating a series of candidates.

A research group led by John Williams has been studying the structure of various antibodies in order to develop a more efficient approach to link compounds to mAbs. Williams is director of the X-ray Crystallography Core Facility, co-director of the Drug Discovery and Structural Biology Core and an associate professor in the Department of Molecular Medicine at the Beckman Research Institute.

In a City of Hope press release in June, Williams' team announced the chance discovery of a peptide-binding site unique to Erbitux cetuximab and then showed that a peptide called a meditope could bind to the site.

Williams' group hypothesized that it might be possible to use the site and meditopes as a convenient means to attach different compounds to a mAb by first conjugating a compound to a meditope.

Eli Lilly and Co., Bristol-Myers Squibb Co....

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