A blocking antibody is an

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

that does not have a reaction when combined with an

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

, 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 The hook effect refers to the prozone phenomenon, also known as antibody excess or the Postzone phenomenon, also known as antigen excess. It is an immunology, immunologic phenomenon whereby the effectiveness of antibody, antibodies to form immune c ...

and, agglutination reaction. Blocking antibodies have been described as a mechanism for

HSV-1 Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...

to evade the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...

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 abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

, Graves' disease, and prevent the growth of

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

mosquito Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning " gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "li ...

es.

Cancer treatment

Blocking antibodies have been used in clinical trials of cancer treatments. The blocking antibody

ipilimumab Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system. Cytotoxic T lymphocytes (CTLs) can recogniz ...

has been effectively used in the clinical treatment of melanoma, RCC, and NSCLC with some degree of success. This is accomplished through the blocking of the coinhibitory molecule

CTLA-4 CTLA-4 or CTLA4 (cytotoxic T-lymphocyte-associated protein 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 exp ...

. 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, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regula ...

, 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 irAEs (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 Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism o ...

binding, resulting in reduced cAMP levels in human

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...

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

immunoglobulins An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

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 is ...

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), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

, 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