Towards Development of a Systems PK-PD Model to Characterize Bystander Effect of Antibody-Drug Conjugates (ADCs)

Antibody-drug conjugates (ADCs) is a thriving new class of drugs, which savor the targeting capability of a monoclonal antibody to deliver potent cytotoxic molecules (payload) to antigenic-rich tumor tissues. Although promising, the overall efficacy of ADCs is often impeded by 1) heterogeneous distribution of these molecules within a solid tumor and 2) tumor heterogeneity in antigen expressing (Ag+) cells. However, certain ADCs exhibit bystander effect, a phenomenon where upon internalization in Ag+ cells, released payload can not only kill Ag+ cells but can diffuse into bystanding antigen non-expressing (Ag-) cells and exert their cytotoxicity. Once characterized in a mathematical framework, bystander effect can be leveraged to sustain more homogeneous payload exposures within a solid tumor over a course of ADC therapy. Within this webinar, we will be discussing the experimental strategies and development of a mathematical model to characterize Bystander Effect.