(316g) Oligoteas: A Platform for Multifunctional Antibody Conjugates and Quantification of Intracellular Processes (INVITED SPEAKER)

Antibody drug conjugates (ADCs) are established bioconjugates for tissue-specific delivery of potent therapeutic drugs. As more ADCs get approved or advance to the clinic, more research is needed to understand and improve their potency and safety profile. In this talk, I will discuss new sequence-defined crosslinkers developed by my group, in combination with different site-specific conjugation techniques, to investigate the effect of drug placement on ADC biophysical properties and potency. Additionally, I will also introduce a new synthetic oligothioetheramide (oligoTEA) modality to quantify bond cleavage directly inside of a living cell. This modality involves a reduction-sensitive FRET-based cross-linker that can be readily conjugated to any targeting ligand, particularly antibody-based ligands. This reduction sensitive antibody-probe conjugate was used along with a mass-action kinetic model and live-cell flow cytometry experiments to quantitate the rate constant for intracellular bond cleavage. The analysis described in this work can be performed as a function of any bond type (plug-and-play), endocytosis pathway, and cell type. In this way, intracellular bond degradation will emerge as a new fundamental parameter to understand the intracellular processing of stimuli-responsive drug carriers and enable the rational design of new drug delivery systems.