In this webinar, you will learn:
- Low-density pMHC immobilization as a strategy to obtain valid monovalent affinity from a bivalent binder under limited antigen supply.
- Application of this SPR method to rank a panel of affinity-matured pMHC binders and select a lead candidate by monovalent affinity.
- Direct translation of SPR-based lead selection into incorporation of the selected binder into a trispecific T cell engager format.
Abstract
T-Cell Engagers are a powerful tool in many cancers but face challenges around target specificity and heterogeneity in solid tumors. Peptide-Major Histocompatibility Complex (pMHC) targets offer a solution to this challenge due to a lack of expression in healthy tissue, while still offering a wide therapeutic window.
Following discovery of a set of novel pMHC binders, selection and affinity maturation, a robust assay was required for measuring affinity. Measuring monovalent affinity of a bivalent binder against a limited-supply pMHC antigen presented an SPR challenge. We resolved this by immobilizing pMHC at low surface density, restricting single binding events per molecule and eliminating avidity-driven affinity artifacts while conserving material. This approach was used to determine monovalent affinities across a panel of pMHC binders discovered and affinity matured for this program, enabling direct ranking and selection of lead candidates for incorporation into a trispecific T cell engager. This presentation outlines the SPR strategy and its application to lead selection for pMHC-directed multispecific engager development.
Speaker Bios
Serah Kimani, PhD
Senior Protein Scientist, Stereo Biotherapeutics
Serah joined Stereo Biotherapeutics this year to build and lead protein production and analytics efforts. In this role, she has established protein expression and purification workflows for discovered molecules spanning monomers to trispecifics, alongside robust protein analytics and developability assessment capabilities.
Prior to joining Stereo, Serah worked for five years as an R&D Scientist at The Structural Genomics Consortium (SGC) in Toronto within industry-partnered biomolecular discovery teams. There she drove projects that contributed to the identification and development of many novel therapeutic binders to pathogenic proteins.
Rosalin Dubois
SPR Expert, Rapid Novor
Rosalin Dubois manages Surface Plasmon Resonance (SPR) Services at Rapid Novor, specializing in biomolecular interaction analysis, kinetic screening, assay development/optimization and data analysis for early-stage drug discovery. She leads high-sensitivity SPR projects to evaluate the binding kinetics and affinity of complex biologics, including multi-specific antibody constructs. Rosalin holds a degree in Life Sciences from Queen’s University, and has characterized over 800 unique interactions by SPR. Whether she’s troubleshooting a challenging assay or planning her next adventure, Rosalin thrives on solving intricate problems.
Serah Kimani, PhD
Senior Protein Scientist, Stereo Biotherapeutics
Serah joined Stereo Biotherapeutics this year to build and lead protein production and analytics efforts. In this role, she has established protein expression and purification workflows for discovered molecules spanning monomers to trispecifics, alongside robust protein analytics and developability assessment capabilities.
Prior to joining Stereo, Serah worked for five years as an R&D Scientist at The Structural Genomics Consortium (SGC) in Toronto within industry-partnered biomolecular discovery teams. There she drove projects that contributed to the identification and development of many novel therapeutic binders to pathogenic proteins.
Rosalin Dubois
SPR Expert, Rapid Novor
Rosalin Dubois manages Surface Plasmon Resonance (SPR) Services at Rapid Novor, specializing in biomolecular interaction analysis, kinetic screening, assay development/optimization and data analysis for early-stage drug discovery. She leads high-sensitivity SPR projects to evaluate the binding kinetics and affinity of complex biologics, including multi-specific antibody constructs. Rosalin holds a degree in Life Sciences from Queen’s University, and has characterized over 800 unique interactions by SPR. Whether she’s troubleshooting a challenging assay or planning her next adventure, Rosalin thrives on solving intricate problems.