Data presented in an abstract at the annual meeting of the American Association for Cancer Research (AACR), taking place April 18-22, 2015 in Philadelphia, validates the use of Meditope Biosciences‘ (San Diego, CA) proprietary SnAP (Site-specific novel Antibody Platform) technology for the development of antibody-drug conjugates (ADCs).

Discovered by a team of researchers led by John Williams, PhD, of the Beckman Research Institute at the City of Hope, a National Cancer Institute (NCI) designated Comprehensive Cancer Center, the SnAP technology can be best compared as turning antibodies into Lego®-like pieces that can be combined with other pieces to expand functionality by easily attach and detach (‘snap‘) anything imaginable on (or off) an antibody without the need for chemical conjugation.  This unique, proprietary, site-specific, platform technology has the potential to advance the antibody market by producing an array of new therapeutic and diagnostic products.

Unique technology
The patented SnAP technology is based on the simple discovery that a naturally occurring pocket of space in the Fab region of antibodies can be engineered to accommodate another molecule, typically a small peptide, directly into that space. Because it nestles itself in that pocket of space, such a molecule is called a meditope.

By switching out a few amino acids in that pocket of space in the Fab region, any antibody can be meditope-enabled. Meditope Biosciences’ technology also includes the meditopes or cyclic peptides, designed to fit into that enabled pocket or space and bind the Fab fragment noncovalently outside the paratope in this novel and unique site. Simply said, the meditope acts as linker-piece which is “snapped” like a piece of Lego® into the naturally occurring pocket of space in the Fab region.

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Once an antibody is enabled, meditopes of varying affinity can be designed to fit in this space with specificity. This unique property makes it possible to ‘conjugate’ cytotoxic payloads to an antibody in a site-specific and consistent manner.

Because each antibody has two Fab regions, two meditope-enabled sites per antibody can be created. This results in a consistent meditope-to-antibody ratio or MAR of 2:1.

No need for complex chemistry
In addition to its simplicity, the SnAP technology avoids the complex chemistry required in other conjugation processes. Rather, a payload can easily be attached to the meditope-linker, which in turn snaps into its binding site on the meditope-enabled antibody.

The available data further shows that neither the meditope-enablement of the antibody nor the binding of a meditope (with or without a payload) to the meditope-enabled antibody interferes with the antibody’s ability to attach to its target.

In the presented research, the scientists looked into peptide modifications to increase meditope’s affinity for a specific antibody, and evaluated the transferability of this approach onto a panel of human antibodies of therapeutic relevance. Their data demonstrated the structures and binding characteristics of a panel of “meditope-enabled” antibodies using the SnAP technology platform and confirmed the versatility of the SnAP technology for conjugation of payloads at a single site on each Fab fragment outside its antigen-binding site. [1]

No interference
Scientists at the company demonstrated the successful transplantation of the meditope binding site to several antibodies. Based on their results, meditope-peptides of different affinities were selected by rational design and fine-tuned according to the requirements of specific application. For ADC development, the data showed that the meditope-peptides are conjugated with cytotoxic payloads (including MMAE and DM-1) and the higher the affinity of the meditope-peptide-drug conjugate for the antibody, the higher the complex’s cytotoxic potential against antigen-positive tumor cells.

These complexes were tested in vitro in a panel of tumor cell lines, to measure and rank the efficacy of the leads in for further development as potential novel oncology therapeutics.

Large number of commercial applications
“We are highly enthusiastic about the data [we’ve presented at the AACR meeting] which point to the many commercial applications that may be possible for our unique SnAP technology, including its potential to develop a powerful new generation of antibody-drug conjugate therapies,” noted Elisabeth Gardiner, Meditope Biosciences’ Chief Scientific Officer and an author of the abstract. “Additionally, the attributes of these ADCs, which use SnAP technology, suggest a less complex, more efficient and predictable manufacturing approach, which can offer significant efficiencies in the drug development process,” she concluded.

Gardiner als noted that the SnAP technology can be applied beyond ADCs, including the development of bi-specific antibodies, in which the meditope-connector piece snaps two different antibodies to each other.  Furthermore, the technology also allows for a simpler development of specific diagnostics, theranostics and research tools.

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