Ibritumomab – Research Grade Biosimilar

Background:

Ibritumomab is a monoclonal antibody directed against the CD20 antigen found on pre-B and mature B lymphocytes (normal and malignant). Ibritumomab binding induces apoptosis in B lymphocytes in vitro. It is combined with the chelator tiuxetan, which acts as a specific chelation site for Yttrium-90 (Y-90). The monoclonal antibody acts as a delivery system to direct the radioactive isotope to the targeted cells, however, binding has been observed in lymphoid cells throughout the body and in lymphoid nodules in organs such as the large and small intestines. Beta-emission induces cellular damage through the formation of free radicals (in both target cells and surrounding cells). B-lymphocyte antigen CD20 is also known as B-lymphocyte surface antigen B1, Leukocyte surface antigen Leu-16, Membrane-spanning 4-domains subfamily A member 1 and MS4A1, is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase (CD45R+, CD117+) and progressively increasing in concentration until maturity. CD20 is expressed on all stages of B cell development except the first and last; it is present from late pro-B cells through memory cells, but not on either early pro-B cells or plasma blasts and plasma cells. It is found on B-cell lymphomas, hairy cell leukemia, B-cell chronic lymphocytic leukemia, and melanoma cancer stem cells. The protein has no known natural ligand and its function is to enable optimal B-cell immune response, specifically against T-independent antigens. It is suspected that it acts as a calcium channel in the cell membrane. CD20 / MS4A1 is the target of the monoclonal antibodies (mAb) rituximab, Ibritumomab tiuxetan, and tositumomab, which are all active agents in the treatment of all B cell lymphomas and leukemias. Defects in CD20 / MS4A1 are the cause of immunodeficiency common variable type 5 (CVID5); also called antibody deficiency due to CD20 defect. CVID5 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen.