ATC Group: L04AG Monoclonal antibodies

Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 21-28 kD lymphocyte cell surface glycoprotein (CD52) expressed primarily on the surface of normal and malignant peripheral blood B and T cell lymphocytes. Alemtuzumab acts through antibody-dependent cellular cytolysis and complement-mediated lysis following cell surface binding to CD52, a cell surface antigen present at high levels on T (CD3+) and B (CD19+) lymphocytes, and at lower levels on natural killer cells, monocytes, and macrophages.

Anifrolumab is a human immunoglobulin G1 kappa monoclonal antibody that binds to subunit 1 of the type I interferon receptor (IFNAR1) with high specificity and affinity. This binding inhibits type I IFN signalling thereby blocking the biologic activity of type I IFNs. Inhibition of type I IFN blocks plasma cell differentiation and normalises peripheral T-cell subsets, restoring the balance between adaptive and innate immunity that is dysregulated in SLE.

Belimumab is a human IgG1λ monoclonal antibody specific for soluble human B Lymphocyte Stimulator protein (BLyS, also referred to as BAFF and TNFSF13B). Belimumab blocks the binding of soluble BLyS, a B cell survival factor, to its receptors on B cells. Belimumab by binding BLyS inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

Efalizumab is a recombinant humanized monoclonal antibody that binds specifically to the CD11a subunit of LFA-1 (lymphocyte function-associated antigen-1), a leukocyte cell surface protein. By this mechanism, efalizumab inhibits the binding of LFA-1 to ICAM-1, which interferes with T lymphocytes adhesion to other cell types. By preventing LFA-1/ICAM binding, efalizumab may alleviate signs and symptoms of psoriasis by inhibiting several stages in the immunologic cascade.

Emapalumab is a monoclonal antibody that binds to and neutralizes interferon gamma (IFNγ). Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of HLH by being hypersecreted.

Natalizumab is a selective adhesion-molecule inhibitor and binds to the α4-subunit of human integrins, which is highly expressed on the surface of all leukocytes, with the exception of neutrophils.

Ocrelizumab is a recombinant humanised monoclonal antibody that selectively targets CD20-expressing B cells. The precise mechanisms through which ocrelizumab exerts its therapeutic clinical effects in MS is presumed to involve immunomodulation through the reduction in the number and function of CD20-expressing B cells. Following cell surface binding, ocrelizumab selectively depletes CD20-expressing B cells through antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. The capacity of B-cell reconstitution and preexisting humoral immunity are preserved.

Rozanolixizumab is a humanised IgG4 monoclonal antibody that decreases serum IgG concentration by inhibiting the binding of IgG to FcRn, a receptor that under physiological conditions protects IgG from intracellular degradation and recycles IgG back to the cell surface. By the same mechanism, rozanolixizumab decreases the concentration of pathogenic IgG autoantibodies associated with generalised myasthenia gravis (gMG).

Ublituximab is a chimeric monoclonal antibody that selectively targets CD20-expressing cells. CD20 is a cell surface antigen found on pre-B cells, mature and memory B cells but not expressed on lymphoid stem cells and plasma cells. The binding of ublituximab to CD20 induces lysis of CD20+ B cells.

Vedolizumab is a gut-selective immunosuppressive biologic. It is a humanised monoclonal antibody that binds specifically to the α₄β₇ integrin, which is preferentially expressed on gut homing T helper lymphocytes. By binding to α₄β₇ on certain lymphocytes, vedolizumab inhibits adhesion of these cells to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), but not to vascular cell adhesion molecule-1 (VCAM-1).