CD20
Encyclopedia
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein
expressed on the surface of all B-cells beginning at the pro-B phase (CD45
R+, CD117
+) and progressively increasing in concentration until maturity.
In humans CD20 is encoded by the MS4A1 gene
.
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
.
, B-cell chronic lymphocytic leukemia
, and melanoma cancer stem cell
s.
Immunohistochemistry
can be used to determine the presence of CD20 on cells in histological
tissue sections. Because CD20 remains present on the cells of most B-cell neoplasms, and is absent on otherwise similar appearing T-cell neoplasms, it can be very useful in diagnosing conditions such as B-cell lymphomas and leukaemias. However, the presence or absence of CD20 in such tumours is not relevant to prognosis, with the progression of the disease being much the same in either case. CD20 positive cells are also sometimes found in cases of Hodgkins disease, myeloma, and thymoma
.
Antibody FMC7 appears to recognise a conformational variant of CD20
also known as the FMC7 antigen.
(mAb) rituximab
, Ibritumomab tiuxetan
, and tositumomab
, which are all active agents in the treatment of all B cell lymphoma
s and leukemias.
The anti-CD20 mAB Ofatumumab
(Genmab
) was approved by FDA in Oct 2009 for Chronic lymphocytic leukemia
.
Additional anti-CD20 antibody therapeutics under development (phase II or III clinical trials in 2008) include :
's B cells and diabetes mellitus
has been determined. In cases of obesity
, the presence of fatty tissues surrounding the body's major organ systems results in cell necrosis
and insulin desensitivity along the boundary between them. Eventually, the contents of fat cells that would otherwise have been digested by insulin are shed into the bloodstream. An inflammation
response that mobilizes both T and B cells results in the creation of antibodies against these cells, causing them to become less responsive to insulin
by an as-yet unknown mechanism and promoting hypertension
, hypertriglyceridemia
, and arteriosclerosis
, hallmarks of the metabolic syndrome
. Obese mice administered anti-B cell CD-20 antibodies, however, did not become less responsive to insulin and as a result did not develop diabetes mellitus or the metabolic syndrome, the posited mechanism being that anti-CD20 antibodies rendered the T cell antibodies dysfunctional and therefore powerless to cause insulin desensitivity by a B cell antibody-modulated autoimmune response. The protection afforded by anti-CD-20 lasted approximately forty days--the time it takes the body to replenish its supply of B cells--after which repetition was necessary to restore it. Hence it has been argued that obesity be reclassify as an autoimmune disease
rather than a purely metabolic one and focus treatment for it on immune system modulation.
Phosphoprotein
Phosphoproteins are proteins that are physically bonded to a substance containing phosphoric acid . This category of organic molecules includes Fc receptors, Ulks, Calcineurins, K chips, and urocortins....
expressed on the surface of all B-cells beginning at the pro-B phase (CD45
CD45
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene. PTPRC is also known as CD45 antigen , which was originally called leukocyte common antigen.- Function :The protein encoded by this gene is a member of the protein tyrosine...
R+, CD117
CD117
Mast/stem cell growth factor receptor also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117 is a protein that in humans is encoded by the KIT gene...
+) and progressively increasing in concentration until maturity.
In humans CD20 is encoded by the MS4A1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
The protein has no known natural ligandLigand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
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
Calcium channel
A Calcium channel is an ion channel which displays selective permeability to calcium ions. It is sometimes synonymous as voltage-dependent calcium channel, although there are also ligand-gated calcium channels.-Comparison tables:...
in the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
.
Expression
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 leukemiaHairy cell leukemia
Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia...
, B-cell chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
, and melanoma cancer stem cell
Cancer stem cell
Cancer stem cells are cancer cells that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic , perhaps in contrast to other non-tumorigenic cancer cells...
s.
Immunohistochemistry
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
can be used to determine the presence of CD20 on cells in histological
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
tissue sections. Because CD20 remains present on the cells of most B-cell neoplasms, and is absent on otherwise similar appearing T-cell neoplasms, it can be very useful in diagnosing conditions such as B-cell lymphomas and leukaemias. However, the presence or absence of CD20 in such tumours is not relevant to prognosis, with the progression of the disease being much the same in either case. CD20 positive cells are also sometimes found in cases of Hodgkins disease, myeloma, and thymoma
Thymoma
Thymoma is a tumor originating from the epithelial cells of the thymus. Thymoma is an uncommon tumor, best known for its association with the neuromuscular disorder myasthenia gravis. Thymoma is found in 15% of patients with myasthenia gravis. Once diagnosed, thymomas may be removed surgically...
.
Antibody FMC7 appears to recognise a conformational variant of CD20
also known as the FMC7 antigen.
Clinical significance
CD20 is the target of the monoclonal antibodiesMonoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
(mAb) rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
, Ibritumomab tiuxetan
Ibritumomab tiuxetan
Ibritumomab tiuxetan, sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for some forms of B cell non-Hodgkin's lymphoma, a lymphoproliferative disorder and thus affects the lymphatic system...
, and tositumomab
Tositumomab
Tositumomab is a drug for the treatment of follicular lymphoma. It is a IgG2a anti-CD20 monoclonal antibody derived from immortalized mouse cells....
, which are all active agents in the treatment of all B cell lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
s and leukemias.
The anti-CD20 mAB Ofatumumab
Ofatumumab
Ofatumumab is a human monoclonal antibody which appears to inhibit early-stage B lymphocyte activation...
(Genmab
Genmab
Genmab A/S is a Danish biotechnology company, founded in February 1999 and based in Copenhagen. Internationally, it operates through the subsidiaries Genmab BV in Utrecht, The Netherlands, and Genmab, Inc in Princeton, New Jersey, USA. The Company is publicly traded on the NASDAQ OMX Copenhagen A/S...
) was approved by FDA in Oct 2009 for Chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
.
Additional anti-CD20 antibody therapeutics under development (phase II or III clinical trials in 2008) include :
- AME-133v (by Applied Molecular Evolution),
- OcrelizumabOcrelizumabOcrelizumab is a humanized anti-CD20 monoclonal antibody. It targets mature B lymphocytes and hence is an immunosuppressive drug candidate. It is under development by Hoffmann–La Roche's subsidiary Genentech, and Biogen Idec....
for multiple sclerosisMultiple sclerosisMultiple 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...
(rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
discontinued in 2010), - TRU-015 (by TrubionTrubionTrubion was a publicly held biopharmaceutical company that was focused on creating a pipeline of protein-based therapeutic product candidates to treat autoimmune and inflammatory diseases and cancer. Trubion was acquired by Emergent BioSolutions on October 28, 2010...
), (discontinued in 2010) - IMMU-106 (veltuzumabVeltuzumabVeltuzumab is a monoclonal antibody which is being investigated for the treatment of non-Hodgkin's lymphoma. , it is undergoing Phase I/II clinical trials.This drug was developed by Immunomedics, Inc....
).
B cells, CD20, and diabetes mellitus
A link between the immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
's B cells and diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
has been determined. In cases of obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, the presence of fatty tissues surrounding the body's major organ systems results in cell necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
and insulin desensitivity along the boundary between them. Eventually, the contents of fat cells that would otherwise have been digested by insulin are shed into the bloodstream. An inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
response that mobilizes both T and B cells results in the creation of antibodies against these cells, causing them to become less responsive to insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
by an as-yet unknown mechanism and promoting hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, hypertriglyceridemia
Hypertriglyceridemia
In medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia . It can also lead to pancreatitis in excessive concentrations In medicine,...
, and arteriosclerosis
Arteriosclerosis
Arteriosclerosis refers to a stiffening of arteries.Arteriosclerosis is a general term describing any hardening of medium or large arteries It should not be confused with "arteriolosclerosis" or "atherosclerosis".Also known by the name "myoconditis" which is...
, hallmarks of the metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
. Obese mice administered anti-B cell CD-20 antibodies, however, did not become less responsive to insulin and as a result did not develop diabetes mellitus or the metabolic syndrome, the posited mechanism being that anti-CD20 antibodies rendered the T cell antibodies dysfunctional and therefore powerless to cause insulin desensitivity by a B cell antibody-modulated autoimmune response. The protection afforded by anti-CD-20 lasted approximately forty days--the time it takes the body to replenish its supply of B cells--after which repetition was necessary to restore it. Hence it has been argued that obesity be reclassify as an 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...
rather than a purely metabolic one and focus treatment for it on immune system modulation.