Human Anti-mouse Antibody
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Human anti-mouse antibody or human anti-murine antibody (HAMA) 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 ...
found in humans which reacts to immunoglobins found in mice.


The HAMA response

Antibody treatment is a type of therapy that is used to treat certain types of
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 ...
and
immune disorder An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways: * By the component(s) of the immune system affected * By whether the immune system is overactive or underactive * By whether t ...
s. Antibodies are proteins which are naturally formed by the body in response to a foreign substance, known as 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 ...
. Antibodies can also be grown outside of the patient’s body and injected into them to help aid the immune system to fight disease. These types of antibodies are typically called monoclonal antibodies because they are created to target one specific antigen.
Herceptin Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wi ...
and
Avastin Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (Intravenous therapy, intravenous) and use ...
, two widely used cancer fighting drugs, are examples of monoclonal antibodies. For several decades, and until recently, mice were used extensively in the production of monoclonal antibodies (MAbs). But the treatments were not as effective as doctors had hoped. One problem was that patients reacted to the mouse antibodies as if they were a foreign substance, and created a new set of antibodies to the mouse antibodies. Doctors have termed this the “HAMA response,” referring to the development of Human Anti-Mouse Antibodies (HAMA). The HAMA response is essentially an
allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
to the mouse antibodies that can range from a mild form, like a
rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, c ...
, to a more extreme and life-threatening response, such as
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
. HAMA can also decrease the effectiveness of the treatment, or create a future reaction if the patient is given a subsequent treatment containing mouse antibodies. It has been observed that anywhere from one-third to more than half of patients receiving mouse-derived antibodies will develop some form of HAMA response. Even more startling, at least ten percent of the general population has been observed to carry some form of animal-derived antibodies, most often from mice, due to the preponderance of medical agents made from the serum of animals. Monoclonal antibodies can be generated for human use without mice by using
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
techniques. MAbs manufactured using these methods do not suffer from the drawbacks related to the HAMA response. Animal protection groups fought for years to end MAb production in mice because it causes intense suffering for the animals that includes severe abdominal pain, difficulty breathing and death. It took considerable, sustained pressure from animal welfare groups, led by legal efforts initiated by the American Anti-Vivisection Society, before this would change. Today in vitro methods of MAb production are recognized and promoted by the National Institutes of Health and are required of all investigators who receive federal funding if their work involves producing MAbs. The existence of HAMA can complicate laboratory measurements. HAMA interferences can give false positive or negative immunoassay results. HAMA bridging interference produces artificially higher results because HAMA's bind to immobilized mouse antibodies in place of substrate, secondary labeled antibodies will then bind to HAMA and produce a positive signal falsely indicative of substrate presence. In this manner, HAMA provides a bridge between immobilized antibodies and labeled secondary antibodies. In contrast, HAMA blocking interference produces no signal for substrate presence when substrate is present. HAMAs will capture immobilized mouse antibodies. In the heterogeneous immunoassay the separation step will wash away the free substrate unable to bind due to HAMA blocking; only the immobilized mouse antibodies and the HAMA remain in the immunoassay when the labeled secondary antibodies are administered. Since the substrate will no longer be able to bind to the immobilized mouse antibodies because of HAMA interference, labeled secondary antibodies will not give a signal for substrate presence.


References

{{reflist, 2 Therapeutic antibodies Monoclonal antibodies Antibodies