anti-CD166 probody-drug conjugate CX-2009

A probody drug conjugate (PDC) composed of a recombinant antibody targeting the tumor-associated antigen (TAA) CD166, which is masked by a cleavable masking peptide, and conjugated to the cytotoxic agent maytansinoid DM4, with potential antineoplastic activity. Upon administration of CX-2009 and migration to the tumor microenvironment (TME), the cleavable masking peptide, which prevent anti-CD166 antibody binding to the CD166 expressed on both normal cells and tumor cells, is proteolytically cleaved by tumor-associated proteases that are specifically present in the TME. This enables the anti-CD166 antibody moiety of CX-2009 to selectively bind to, be internalized by, and deliver DM4 into CD166-expressing tumor cells. Following internalization, DM4 is released, binds to tubulin and disrupts microtubule assembly/disassembly dynamics, resulting in inhibition of cell division and cell growth of CD166-expressing tumor cells. The masking peptide prevents binding of the anti-CD166 antibody to CD166 in normal tissues, thereby minimizing toxicities.