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TM4SF1-cMET bispecific ADC is a first-in-class bispecific antibody-drug conjugate (ADC) developed by Tavotek Biotherapeutics for the treatment of various solid tumors. This biologic modality simultaneously targets two proteins: TM4SF1 (Transmembrane-4-L-six-family member-1), a member of the tetraspanin superfamily that is overexpressed in many cancers and associated with cancer stem cells and tumor angiogenesis, and cMET (Hepatocyte Growth Factor Receptor), a receptor tyrosine kinase often dysregulated in malignancy. The ADC utilizes a bispecific antibody backbone conjugated to the cytotoxic payload monomethyl auristatin E (MMAE) with a drug-to-antibody ratio (DAR) of 4. By dual-targeting these distinct tumor-associated antigens, the agent aims to improve tumor selectivity and internalization while mitigating resistance mechanisms common to single-target therapies. Preclinical studies have demonstrated potent tumor growth inhibition across multiple cancer types, including pancreatic, gastric, lung, ovarian, and triple-negative breast cancers (TNBC).
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