anti-CD33/BET degrader ADC ABBV-787

An antibody-drug conjugate (ADC) consisting of a monoclonal antibody directed against the tumor-associated antigen (TAA) CD33 conjugated to a bromodomain and extra-terminal domain (BET) degrader payload, with potential antineoplastic activity. Upon administration of anti-CD33/BET degrader ADC ABBV-787, the monoclonal antibody portion of ABBV-787 specifically targets and binds to the cell surface antigen CD33 expressed on myeloid leukemia cells. Upon internalization, the BET degrader payload is released and leads, through an as of yet not fully elucidated mechanism, to the degradation of BET proteins by the ubiquitin-proteasome system. This dysregulates gene expression and specifically leads to the downregulation of the expression of certain growth-promoting genes, which may inhibit the proliferation of BET-overexpressing and CD33-expressing tumor cells. CD33 is expressed on normal non-pluripotent hematopoietic stem cells and myeloid leukemia cells. BET family of proteins, comprised of bromodomain-containing proteins 2 (BRD2), 3 (BRD3), and 4 (BRD4) as well as bromodomain testis-specific protein (BRDT), are transcriptional regulators that are overexpressed in certain tumor cells and play important roles during cellular development and growth.