Atacicept
Encyclopedia
Atacicept is a recombinant fusion protein designed to inhibit B cell
s, thereby suppressing autoimmune disease
. The designer protein combines the binding site for two cytokine
s that regulate maturation, function, and survival of B cells, B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), with the constant region of immunoglobin. Atacicept blocks activation of B cells by the tumor necrosis factor receptor superfamily member 13B (more commonly known as TACI), a transmembrane receptor protein found predominantly on the surface of B cells. Like the monoclonal antibody belimumab
, atacicept blocks the binding of BLyS, but it also blocks APRIL. Binding of these TACI ligands induces proliferation, activation, and longevity of B cells and thus their production of autoantibodies. Atacicept is thought to selectively impair mature B cells and plasma cells with less impact on progenitor cell
s and memory B cell
s.
Studies have looked at atacicept in animal models of autoimmune disease and in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and optic neuritis. A phase II/III trial for systemic lupus erythematosus
is due to run from 2008 to 2012. The subcutaneously injected protein failed a phase II trial for multiple sclerosis
. The trials of atacicept in people with MS were suspended when some people taking the drug in one trial had an unexpected increase in inflammatory activity. An independent data monitoring board for the MS study found "subjects receiving atacicept were having more relapses and new MRI lesions than those on the placebo."
The drug is also being studied for treatment of B-cell malignancies, including multiple myeloma
, B-cell chronic lymphocytic leukemia, and non-Hodgkin's lymphoma.
Atacicept was developed by a Seattle-based biotech company, ZymoGenetics, which handed the product over to Merck Serono for further development.
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s, thereby suppressing autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
. The designer protein combines the binding site for two cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s that regulate maturation, function, and survival of B cells, B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), with the constant region of immunoglobin. Atacicept blocks activation of B cells by the tumor necrosis factor receptor superfamily member 13B (more commonly known as TACI), a transmembrane receptor protein found predominantly on the surface of B cells. Like the monoclonal antibody belimumab
Belimumab
Belimumab is a fully human monoclonal antibody that inhibits B-lymphocyte stimulator , also known as B cell activation factor of the TNF family...
, atacicept blocks the binding of BLyS, but it also blocks APRIL. Binding of these TACI ligands induces proliferation, activation, and longevity of B cells and thus their production of autoantibodies. Atacicept is thought to selectively impair mature B cells and plasma cells with less impact on progenitor cell
Progenitor cell
A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell...
s and memory B cell
Memory B cell
Memory B cells are a B cell sub-type that are formed following primary infection.-Primary response, paratopes, and epitopes:In wake of first infection involving a particular antigen, the responding naïve cells proliferate to produce a colony of cells, most of which differentiate into the plasma...
s.
Studies have looked at atacicept in animal models of autoimmune disease and in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and optic neuritis. A phase II/III trial for systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
is due to run from 2008 to 2012. The subcutaneously injected protein failed a phase II trial for multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
. The trials of atacicept in people with MS were suspended when some people taking the drug in one trial had an unexpected increase in inflammatory activity. An independent data monitoring board for the MS study found "subjects receiving atacicept were having more relapses and new MRI lesions than those on the placebo."
The drug is also being studied for treatment of B-cell malignancies, including multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
, B-cell chronic lymphocytic leukemia, and non-Hodgkin's lymphoma.
Atacicept was developed by a Seattle-based biotech company, ZymoGenetics, which handed the product over to Merck Serono for further development.