Antibody Therapeutics Xchange - San Diego - 2025

Overcoming complex therapeutic challenges requires next-gen precision and targeting for maximum efficacy, something that is often addressed by pursuing de novo antibody design. However, in silico antibody discovery models need accurate, high-resolution empirical structural data to correctly predict effective epitope/paratope interactions, especially for de novo antibody design. Here, we introduce an innovative approach that utilizes high-throughput, high-resolution analysis of higher-order structure (HOS) through radical footprinting mass spectrometry, enabling rapid, accurate characterization of epitopes/paratopes, conformational changes, and higher-order structure to generate a bespoke database of large libraries of antibody/antigen interactions. 

We then use these data to inform selection of binders with the greatest therapeutic potential. Through a combination of high throughput structural screening and empirically-constrained computational modeling, we systematically engineered antibodies that bind to a critical epitope on Human Fibroblast Activating Protein (hFAP), a historically challenging target, with exceptional affinity and specificity.

Efficient bispecific antibody (bsAb) production requires precise assembly of multiple chains. Combin ...

The antibody response to vaccination and infection is key to immune defense and human antibody therapeutic development, offering a blueprint for targeted treatments. While B-cell sequencing aids human antibody discovery, it may miss the full diversity of circulating antibodies, as only 2-3% of B cells are in circulation, and not all produce antibodies. We demonstrate a mass spectrometry proteomics-based approach to sequencing neutralizing antibodies from serum of a patient vaccinated against SARS-CoV-2. Following de novo sequencing, we recombinantly expressed 12 antibodies. Six recombinant antibodies exhibited similar or higher binding affinities than the original natural polyclonal antibody and exhibited neutralizing capabilities.

Combatting deconjugation of linker-payloads through next-generation conjugation site chemistries. Co ...

What are the key considerations for target selection to enhance ADC efficacy? What should be the pay ...

Does antibody pharmacology matter, and why? Is there a “right” scaffold for a specific functional go ...

Optimizing protein therapeutics for clinical success: How can incorporating developability assessmen ...

Why is gathering high-quality structural data in early screening critical to speeding up development ...

Is broad-based use of conventional IgG somewhat limited by its fundamental biophysical properties? A ...

What are the key issues faced in the in vitro degradation of antibodies, and which (bio)chemical pat ...

What challenge do ADCs face due to the presence of target antigens on healthy cells? How does hetero ...

Overcoming complex therapeutic challenges requires next-gen precision and targeting for maximum efficacy. Conventional discovery approaches fall short since they are not guided by structure and are thereby limited in their ability to target specific epitopes. We introduce a novel approach: by leveraging high-throughput, high-resolution structure determination, we systematically engineer high-affinity antibodies that selectively bind a target epitope— ensuring exceptional precision and efficacy against even unstructured, multimeric or otherwise structurally challenging targets.