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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 praluzatamab ravtansine 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.
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