Many immunotherapies adapt to solve the field’s most pressing issues (an intricate balance between persistence, potency, and safety) by integrating multiple signaling mechanisms and engaging with more than one target in parallel. With that trend, the binding mechanisms between binder and target also complexify.
Yet, most binding assays haven’t kept up.
Target cells (adherent or non-adherent) are generally of two types:
Introduction of labeled binders to the uniform monolayer. These can include:
Controlled force applied to the bound cells probes the strength of interactions between labeled and target populations.
Fluorescence microscopy captures the number of bound cells before and after force application. The percentage of bound cells after force application indicates the population’s Cell Avidity.
Cell Avidity quantifies cell binding with hundreds of cells per measurement.
Integrating Cell Avidity in the drug development workflow leads to faster identification of the most potent, safe and sensitive drug candidate by reducing the required number of design iterations or eliminating candidates from in vivo preclinical studies which ultimately bind ineffectively in a cellular context.
Quickly rank hundreds to thousands of therapeutic candidates to get insights into sensitivity and safety. Incorporate Cell Avidity early in the discovery workflow helps ensure that only candidates with the most promising binding characteristics progress.
Commercial CAR-T therapies still suffer from severe limitations, as majority of patients fail to achieve complete response and ultimately relapse.
Watch this Webinar to discover Prof. Marco Ruella’s team have adopted a novel CAR-T avidity screening method to improve safety and exhaustion profile, leading to 100% clinical response in a phase I trial.
Mechanistic issues limit the effectiveness of many current cancer-targeting antibody therapies, with monospecific antibodies often hindered by receptor dimerization and activation. Biparatopic antibodies, which bind to two unique non-overlapping epitopes, offer a promising solution with stronger binding, more potent antagonism, and higher specificity.