L-DOS47 + doxorubicin

L-DOS47 + doxorubicin is a combination therapy consisting of **L-DOS47**, a clinical-stage antibody-enzyme conjugate (antibody-drug conjugate, or ADC), and **doxorubicin**, an anthracycline chemotherapeutic. L-DOS47 targets carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), which is highly expressed in several tumor types including pancreatic and non-small cell lung cancers. L-DOS47 consists of camelid single-domain antibodies that specifically bind CEACAM6 and are conjugated to jack bean urease. Upon binding to CEACAM6-positive tumor cells, the enzyme converts urea to ammonia and carbon dioxide, elevating the pH and neutralizing the acidic tumor microenvironment (TME). This TME modulation is hypothesized to support immune cell infiltration, boost immunotherapy efficacy, and improve susceptibility to cytotoxic agents. Doxorubicin intercalates DNA and inhibits topoisomerase II, leading to cell death. The combination is under investigation for enhanced anti-tumor activity, particularly in advanced pancreatic cancer[3][5].