Cell growth and regulation involve vast networks of interacting DNAs, RNAs, proteins, lipids and sugars. Through a fundamental strategy of life, these interactions push multiple cellular processes by increasing local concentrations of key molecules. Now scientists can exploit these interactions with a new type of precision therapy called the Extracellular Drug Conjugate (EDC).

EDCs are a new type of ADC that use proximity to activate the drug’s potential. In the case of EDCs, a drugs activity is increased by over 1000-fold if both targets (antibody and drug) are within angstroms apart (i.e. they interact).   This talk will discuss how EDCs can exhibit low to mid-picomolar potencies, and with signal to noise ratios of > 1,000:1; both of which are dependent on the expression and interaction of two proteins.

Specifically, this talk will focus on proteins that interact with the human Na,K-ATPase (NKA). An active plasma membrane ion pump, the NKA is required for life. Without it, the cell cannot maintain a proper ion potential and the cells dies by a natural death process known as necrosis. You will learn about; 1) how a small naturally occurring steroid can be delivered to specific cell types and how this delivery can affect cell growth and cytokine production, 2) how this knowledge can be exploited in precision medicine, and 3) how a blockbuster antibody medicine can be constructed to kill B-cells while having no effect on other blood cells. This talk will therefore describe a new level of therapeutic precision that depends on protein-protein proximity and not simply the expression of a single protein.