A blocking antibody is an

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

that does not have a reaction when combined with an

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

, but prevents other antibodies from combining with that antigen. This function of blocking antibodies has had a variety of clinical and experimental uses. The term can also be used for inhibiting antibody, prozone phenomenon and, agglutination reaction. Blocking antibodies have been described as a mechanism for HSV-1 to evade the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

Uses

Blocking antibodies can be used in a variety of medical and scientific manners, thus far been to treat

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

Graves' disease Graves' disease, also known as toxic diffuse goiter or Basedow's disease, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...

, and prevent the growth of

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

mosquito Mosquitoes, the Culicidae, are a Family (biology), family of small Diptera, flies consisting of 3,600 species. The word ''mosquito'' (formed by ''Musca (fly), mosca'' and diminutive ''-ito'') is Spanish and Portuguese for ''little fly''. Mos ...

es.

Cancer treatment

Blocking antibodies have been used in clinical trials of cancer treatments. The blocking antibody ipilimumab has been effectively used in the clinical treatment of

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

, RCC, and NSCLC with some degree of success. This is accomplished through the blocking of the coinhibitory molecule

CTLA-4 Cytotoxic T-lymphocyte associated protein 4, (CTLA-4) also known as CD152 ( cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA-4 is constitutively expressed in ...

. The blocking antibody does not directly target tumor cells, but rather blocks the regulatory functions of CTLA-4, resulting in enhanced T-cell function. Some new treatments hypothesize the blocking of

PD-1 Programmed cell death protein 1 (PD-1), (CD279 cluster of differentiation 279). PD-1 is a protein encoded in humans by the ''PDCD1'' gene. PD-1 is a cell surface receptor on T cells and B cells that has a role in regulating the immune system's re ...

, a programmed cell-death protein, which will result in longer-lived T-cells. The blocking antibody BMS-936559 has been shown to bind to PD-L1 and prevent its binding to PD-1. These new treatments are not without side-effects and immune-related adverse events have been observed in a variety of patients. The tolerance that immune cells normally have to host tissues can be lost, resulting in permanent damage to host cells.

Graves' disease

Studies have shown that blocking antibodies can bind to and prevent thyrotropin binding, resulting in reduced cAMP levels in human

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

cells. This interaction has been used primarily as a method of indicating that

immunoglobulins An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause di ...

are pluritopic, meaning that they have multiple effects, rather than indicating a possible treatment for this disease.

Malaria

Blocking antibodies have a variety of functions on the

merozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...

form of parasitic malaria. While in the merozoite form, malaria parasites invade erythrocytes and reproduce in them. Some blocking antibodies may inhibit the invasion of

erythrocytes Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

, while other blocking antibodies prevent the binding of inhibitory antibodies, allowing merozoite invasion of erythrocytes despite the presence of inhibitory antibodies. The monoclonal antibodies that prevent the invasion of merozoites bind to the parasitic antigen MSP-1 (merozoite surface protein 1). The binding of blocking antibodies to MSP-1 is shown to result in the inhibition of secondary processing, resulting in the inability for merozoites to invade host erythrocytes. Secondary processing involves a single proteolytic cleavage on the merozoite surface of the carboxy-terminal component of MSP-1. The blocking of MSP-1 has been proposed to be a method of creating a vaccine against malaria by preventing its invasion and multiplication.

References

External links