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Monoclonal antibodies (mAbs) represent the richest, most diverse molecular design space for drug discovery—a fact reflected in mAbs’ popularity. With more than 60 major-market approvals and at least 500 more in development, mAbs enjoy global sales of nearly $125 billion, which is expected to rise to $350 billion by 2027. AbbVie’s Humira (adalimumab) autoimmune therapy is the world’s best-selling drug, raking in $20 billion in 2019.
Antibodies targeting specific epitopes cannot be designed from scratch as with small molecule drugs. Instead, candidate antibodies are mined from large, diverse pools derived from either immunized animals, phage display libraries, or from antibody-producing B
cells. All these methods generate many thousands of mAbs whose suitability for further development varies widely and about which very little is known. Screening large panels of mAbs can be complex and extremely resource intensive.
Surface plasmon resonance (SPR) is used to compare the binding epitope of each antibody, how strongly it binds, and to determine the antibody’s mechanism of action. When a molecule in solution binds to a molecule tethered to the surface of a thin metal film,
the mass increases. This changes the refractive index of the solution near the film’s surface, making it possible to optically detect when binding has occurred.
However, traditional SPR does not have the throughput to match the output of the current generation of mAb expression platforms. High-throughput surface plasmon resonance addresses this unmet need. For example, Carterra’s LSA platform uses sensor chips to study 384 antibodies simultaneously and over 1,100 in one unattended run; the previous gold standard was eight antibodies at a time.
Now you can generate 100 times the data in 10% of the time, using just 1% of the sample required by older platforms.
By screening and characterizing antibodies at the same time, HT-SPR can help researchers identify the best drug candidates from a vast library of antibodies in just hours or days. Deducing which epitope each antibody binds, how strongly it binds, and its mechanism of action make the new techniques mandatory for any lab that wants to keep pace.
For example, researchers have been using HT-SPR to identify therapeutic antibodies that bind to the SARS-CoV-2 spike protein which the virus uses to enter cells. The first COVID-19 therapeutic was discovered, characterized, and sent to the clinic in just 90 days using Carterra’s LSA. That’s the state of the art for biologics discovery.
Biopharmaceutical companies also create transgenic animals that produce a wide range of antibodies. They use Carterra’s LSA to validate new strains of transgenic animals, such as transgenic chickens, to confirm that the animals are producing antibody panels with a lot of diversity in epitope coverage and binding kinetics. Genomics companies also use HT-SPR to screen and characterize antibody libraries.
Contract Research Organizations (CROs) have also leveraged the throughput advantages of Carterra’s new technology. LakePharma Inc., with locations in CA, MA and TX, was an early adopter of the platform. “The LSA gives researchers a tremendous amount of data to
make the right decisions about which leads to advance,” says Dr. Margaret Wong, Senior Director at LakePharma. “Since the installment of the first instrument in 2018, we have doubled our LSA footprint as demand from our clients for these kinds of data has been exponential. We cannot imagine discovery and engineering without it.”
The demand for therapeutic antibodies will continue to grow, including therapies for infectious diseases such as COVID-19. Researchers who can quickly and accurately find the best candidates for the job will have a head start on finding the next blockbuster.
Learn more about Carterra’s high-throughput monoclonal antibody screening and characterization platform at: www.carterra-bio.com