Anti-DLL3 Antibody (Rovalpituzumab)

Rovalpituzumab is a humanized monoclonal antibody against delta like protein 3 (DLL3). Rovalpituzumab can be used in the synthesis of the antibody-drug conjugate (ADC) Rovalpituzumab Tesirine. DLL3, also known as delta like ligand three, is a Notch ligand characterized by a DSL domain, transmembrane region, and a series of EGF repeats. Notch ligands can participate in trans-interactions (interaction with Notch receptor on a different cell) and cis interactions (interaction with Notch receptor within the same cell) to activate or inhibit Notch signaling, respectively. DLL3 exclusively functions to inhibit Notch signaling through cis inhibition. While DLL3 expression is limited in healthy tissue, high expression levels of DLL3 are found in various cancers including small cell lung cancer (SCLC), where it plays an oncogenic role. Relieving DLL3-mediated inhibition of Notch signaling may serve as a therapeutic avenue, with drugs being developed to target DLL3 as a possible lung cancer therapy (example: rovalpituzumab tesirine). The application of ADCs (antibody drug conjugates) is also been evaluated. Rovalpituzumab tesirine, an ADC targeting DLL3, is composed of of the antibody Rovalpituzumab and a cytotoxic agent, was investigated as in clinical trials for SCLC.