PEGS Boston 2021 Recap Series

Aids and Cancer Antibody Engineering, Support from REmAb^® Sequencing

Our core sequencing platform, REmAb®, is a mass spectrometry-based de novo protein sequencing platform. Our clients routinely use REmAb® because they can access the primary amino acid sequence of a monoclonal antibody (mAb) protein sample from any species, no matter the isotype. Most importantly, our platform’s de novo approach enables the full sequencing of the mAb primary amino acid sequence with the highest accuracy without needing to have access to a cell line, or to genomic or transcriptomic data.

Most of REmAb®’s use cases center on monoclonal antibodies used to fight against cancer and infectious diseases, which is why we are always eager to understand more about how these antibodies are engineered and studied. As such, we really looked forward to Dr. Nabel’s talk to see the exciting work that ModeX Therapeutics is doing.

 

Gary J. Nabel – Tackling AIDS and Cancer with trispecific antibodies

Dr. Nabel’s talk focused on ModeX Therapeutics’ potent trispecific antibodies. These antibodies are on the rise in the therapeutic world and will continue being used as they can target more than one epitope. Monoclonal-based therapy of viruses such as HIV typically results in escape mutants, and thus poor treatment outcomes. Unlike monoclonals, trispecifics drastically decrease the possibility of escape mutants arising. Furthermore, they could be delivered to patients in a simpler fashion in contrast to monoclonal cocktails.

Dr. Nabel elaborated on ModeX Therapeutics’ journey in creating successful trispecifics for HIV, and for multiple myeloma. The team initially designed bispecifics with an IgG framework, with two stacked Fv regions, but they found them challenging to manufacture and difficult to manipulate due to their biochemical properties. These limitations prompted them to go back to the drawing board.

They engineered trispecifics with two specificities in one arm, and a single one in the second arm. They compared their bispecifics against their engineered trispecifics. In their 2017 study, they showed that the former were only efficacious against 30% of HIV-1 Clade B viruses, while the latter had the broadest and most potent neutralization activity they had observed in any previously discovered antibody therapeutics against HIV.

Dr. Nabel’s talk once more highlighted the importance of structural knowledge. This is the reason why Dr. Veesler’s group at the University of Washington requested our REmAb services and trusted us with their project on neutralizing antibodies against spillover-prone viruses Nipah and Hendra.

Dr. Nabel also discussed the use of trispecifics in combination for checkpoint inhibitors for diseases like MM. In the past, clients have found novel checkpoint inhibitors using our REmAbⓇ antibody sequencing platform. But other than helping companies find better treatments for cancers, our company is committed to multiple myeloma patients by monitoring for relapse using protein sequencing. We have developed an assay for MM that is the only non-invasive, high-precision one offered in the market. In the future, companies like ModeX Therapeutics could use this service to track treatment outcomes for MM patients during clinical trials. Sensitive monitoring ensures relapse is caught earlier, thus highly improving a patient’s prognosis.

 

Empowering Researchers with Next Generation Protein Sequencing

Attending these talks affirmed our notion that our technology can be immensely helpful for researchers. We look forward to continuing empowering companies’ research and development efforts, such as those spoken by Dr. Ab in successfully engineering potent ADCs, and Dr. Nabel in the discovery of powerful trispecifcs. Rapid Novor’s next generation protein sequencing technology can be applied to any species and any antibody, including trispecifics and multispecifics. You can read more about how our goals can align with yours in this white paper.

 

This Concludes our PEGS Boston 2021 Recap Series…

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