Anti-CD20-Anti-CD3 IgM format Bispecific Antibody

CD20 (MS4A1) is a glycosylated phosphoprotein expressed on the cell surface of B cells. Although the functional significance of CD20 is not clear, and CD20 has no known ligands, CD20 has been shown to regulate intracellular calcium levels. CD20 is a highly attractive target antigen for immunotherapy because it is expressed in more than 90% of patients with B-cell lymphoma. First approved in 1997, Rituximab (Rituxan) is a chimeric monoclonal antibody targeting CD20 and has been classified by the World Health Organization as an “Essential Medicine”. Since then, additional monoclonal antibodies against CD20 have been approved or are being tested in clinical trials for the treatment of multiple sclerosis (MS), chronic lymphocytic leukemia (CLL), follicular lymphoma, diffuse large B cell lymphoma (DLBCL), rheumatoid arthritis, non-Hodgkin’s lymphoma, systemic lupus erythematosus, and myalgic encephalomyelitis (chronic fatigue syndrome) .The IgM pentameric structure is supposed to produce a stronger binding to cells with low expression of CD20, as well as greater ability to cross-link cell surface receptors for increased cellular signaling. In the meantime, because of the ratio of anti CD20- and anti CD3-antibodies, the cytokine release is supposed to be reduced.