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Neural cell adhesion molecule 1 (CD56) is a glycoprotein of the immunoglobulin superfamily that mediates cell-cell adhesion through homophilic and heterophilic interactions (UniProt P13591). It is a primary marker for natural killer (NK) cells and is also expressed on neurons, glia, and skeletal muscle. In oncology, CD56 is frequently overexpressed in malignancies such as small cell lung cancer, multiple myeloma, and neuroblastoma, where it facilitates tumor cell survival and migration. The homophilic interaction between CD56 on NK cells and CD56 on tumor cells is critical for the formation of the immunological synapse, influencing the efficiency of NK cell-mediated cytotoxicity (PMID: 25633483). Therapeutic strategies have focused on exploiting this high expression through antibody-drug conjugates like lorvotuzumab mertansine and experimental CAR-T cell therapies (PMID: 23511374). However, the expression of CD56 in the nervous system presents a significant risk for off-target effects, most notably peripheral neuropathy, which has limited the clinical progression of some CD56-targeted agents.
Targeted delivery of cytotoxic agents via antibody-drug conjugates or direct T-cell mediated lysis via chimeric antigen receptors; modulation of homophilic adhesion to enhance immunological synapse formation.
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