lucanisatuzumab

Lucanisatuzumab is a humanized monoclonal antibody (IgG1 kappa) that targets the solute carrier family 44 member 4 (SLC44A4), also known as AGS-5 or choline transporter-like protein 4. It was primarily developed as the targeting component of the antibody-drug conjugate (ADC) ASG-5ME (also known as AGS-5ME). The ADC consists of lucanisatuzumab conjugated to the potent microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable valine-citrulline linker. SLC44A4 is a cell surface protein that is highly expressed in several epithelial malignancies, including pancreatic, prostate, and gastric cancers, while showing very limited expression in normal tissues. The mechanism of action involves the binding of the antibody to SLC44A4 on the surface of cancer cells, followed by internalization of the ADC and subsequent intracellular release of MMAE, which leads to cell cycle arrest and apoptosis. Clinical development was conducted by Astellas Pharma in collaboration with Seattle Genetics (now Pfizer), but Phase 1 clinical trials for indications such as pancreatic and gastric cancer were terminated.