An antibody-drug conjugate (ADC) consisting of a monoclonal antibody against lysosome-associated membrane protein 1 (LAMP1) conjugated, via the disulfide-containing cleavable linker N-succinimidyl-4-(2-pyridyldithio)butyrate (SPDB), to the cytotoxic maytansinoid DM4, with potential antineoplastic activity. Upon administration of anti-LAMP1 ADC SAR428926, the anti-LAMP1 monoclonal antibody moiety targets and binds to the cell surface antigen LAMP1. After antibody-antigen interaction and internalization, the SPDB linker is selectively cleaved by proteases in the cytosol and the DM4 moiety is released. DM4 binds to tubulin and disrupts microtubule assembly/disassembly dynamics, thereby inhibiting both cell division and cell growth of LAMP1-expressing tumor cells. LAMP1, overexpressed on a variety of cancer cells, plays a key role in cell-cell adhesion and migration. The SPDB linker is resistant to cleavage in the bloodstream, which may increase stability and reduce toxicity. Check for active clinical trials using this agent. (NCI Thesaurus)
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