Summary

Background

This non-therapeutic biosimilar antibody uses the same variable regions as the therapeutic antibody, loncastuximab, making it ideal for research use. Loncastuximab is a humanized IgG1, k monoclonal antibody that reacts with the human B-cell marker CD19, a membrane glycoprotein of the immunoglobulin superfamily that is expressed at the various stages of B-cell development and is detectable in most B-cell malignancies. CD19 is an ideal target for antibody-drug conjugates (ADCs) and other therapies because it plays a key role in lymphocyte biology, is uniquely expressed on B cells, and is rapidly internalized without shedding into the bloodstream. These properties make it especially valuable in research on B cells and relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma. Loncastuximab tesirine is a human CD19-directed ADC, wherein the antibody is conjugated through a cathepsin-cleavable linker to SG3199, a potent pyrrolobenzodiazepine dimer alkylating cytotoxin. Upon binding to CD19 on the cell membrane, the ADC is internalized and transported to lysosomes, where it is cleaved to release the drug inside the cells, ultimately inducing apoptotic cell death through the crosslinking of DNA. In vitro experiments using loncastuximab tesirine in multiple lymphoma cell lines demonstrated this ADC’s strong cytotoxic activity that correlated with the level of CD19 expression. The in vivo treatment of loncastuximab tesirine is also reported to show dose-dependent antitumor activity in human CD19-expressing Burkitt lymphoma-derived Ramos models (subcutaneous as well as disseminated xenograft models involving Ramos and NALM-6 cells).