ABZYMES Submitted by, Jeeva Raj Joseph 1st sem The pathogenic role of DNA abzymes is not quite clear. However Applications 1. Catalytic antibodies (abzymes): From concept to application ABSTRACT The importance of generati ng antibodies to catalyse specific reactions was discussed . Abzymes are these same molecules but with the addition of catalytic activity, a property rarely Potential Clinical Applications Of Abzymes.
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This article throws light upon the four types of applications of monoclonal antibodies. The four types of applications are: Monoclonal antibodies have revolutionized the laboratory diagnosis of various diseases. For this purpose, MAbs may be employed as diagnostic reagents for biochemical analysis or as tools for diagnostic imaging of diseases.
Abzyme – Wikipedia
In recent years, a number of diagnostic kits using MAbs have become commercially available. Cancers estimation of plasma carcinoembryonic antigen in colorectal cancer, and prostate specific antigen for prostate cancer. Besides diagnosis, estimation of tumor markers is also useful for the prognosis of cancers. That is a gradual fall in a specific tumor marker is observed with a reduction in tumor size, following treatment.
Hormonal disorders analysis of thyroxine, triiodothyronine and thyroid stimulating hormone for thyroid disorders. Infectious diseases by detecting the circulatory levels of antigens specific to the infectious agent e.
Radiolabeled—MAbs are used in the diagnostic imaging of diseases, and this technique is referred to as immunoscintigraphy.
The radioisotopes commonly used for labeling MAb are iodine— and technetium— The MAb applicationx with radioisotope are injected intravenously into the applocations. These MAbs localize at specific sites say a tumor which can be detected by imaging the radioactivity. In recent years, single photon emission computed tomography SPECT cameras are used to give a more sensitive three dimensional appearance of the spots localized by radiolabeled— MAbs.
Immunoscintigraphy is a better diagnostic tool than the other imaging techniques such as CT scan, ultrasound scan and magnetic resonance. For instance, immunoscintigraphy can differentiate between cancerous and non-cancerous growth, since radiolabeled—MAbs are tumor specific.
Abzymes: An Introduction
This is not possible with other imaging applicahions. Monoclonal antibodies are successfully used in the diagnostic imaging of cardiovascular diseases, cancers and sites of bacterial infections. The cardiac protein abzymex gets exposed wherever myocardial necrosis death of cardiac cells occurs. Antimyosin MAb labeled with radioisotope indium chloride In is used for detecting myosin and thus the site of myocardial infarction. Imaging of radiolabeled MAb, is usually done after hours of intravenous administration.
This is carried out either by planner gamma camera or single photon emission computed tomography SPECT. It is possible to detect the location and the degree of damage to the heart by using radiolabeled antimyosin MAb. Thus, this technique is useful for the diagnosis of heart attacks. DVT refers to the wbzymes of blood clots thrombus within the blood veins, primarily in the lower extremities.
The imaging is usually done after 4 hours of injection.
Fibrin specific MAbs are successfully used for the detection of clots abzy,es thigh, pelvis, calf and knee regions. Thickening and loss of elasticity of arterial walls is referred to as atherosclerosis. Atherosclerotic plaques cause diseases of coronary and peripheral arteries.
Abzymes: An Introduction | Sussex Drug Discovery Centre
Atherosclerosis has been implicated in the development of heart diseases. MAb tagged with a radiolabel directed against activated platelets can be used to localize the atherosclerotic lesions by imaging technique.
Monoclonal antibodies against many types of human cancers are now available. A selected list of tumor markers along with the associated cancers that can be used for MAb imaging is given in Table Tumors can be located in patients using radioisotope labeled MAbs specific to the protein sparticularly of membrane origin.
It has been possible to detect certain cancers at early stages lung cancer, breast cancer, ovariran cancer, malanoma, colorectal cancer by employing MAbs. About 80 per cent specificity has been achieved appliccations detecting cancers by this approach. An iodine 1 31 l labeled monoclonal antibody specific to breast cancer cells when administered to the patients detects by imaging the spread of cancer metastasis to other regions of the body.
This is not possible by scanning techniques. The imaging technique by using MAb can also be used to monitor therapeutic responses of a abxymes.
There are certain limitations in using MAb in cancer diagnosis and prognosis. These include the difficulty in the selection of a specific MAb and the access of MAb to the target site of the tumor which may be less vascularized. The pathological changes of the cancerous tissue can be detected by immunohistochemical techniques. This can be done by using MAb against a specific antigen. Hematopoietic stem cells in bone marrow are the precursors for different blood cells, B- and T-lymphocytes which are produced in a stepwise transformation.
During malignancy, transformation of lymphocytes stops at a particular stage of maturation. Applicaitons can be detected by using stage- specific MAbs. In recent years, attempts are made to detect the sites of infections by using MAbs. This is made possible by directing MAb against bacterial antigens.
Further, monoclonal antibodies against inflammatory leucocytes which accumulate at infection site are also useful to specifically detect localized infections.
Monoclonal antibodies have a wide ahzymes of therapeutic applications. MAbs are used in the treatment of cancer, transplantation of bone marrow and organs, autoimmune diseases, cardiovascular diseases and infectious diseases. Monoclonal antibodies can be directly used for enhancing the immune function of the host.
Direct use of MAbs causes minimal toxicity to the target tissues or the host. MAbs promote efficient opsonization of pathogenic organisms by coating with antibody and enhance phagocytosis. In fact, MAbs were found to protect chimpanzees against certain viral hepatitis B-virus and bacterial E. MAbs, against the antigens on the surface of cancer cells, are useful for the treatment of cancer.
The antibodies bind abzyms the cancer cells and destroy them. This is brought out by antibody—dependent cell-mediated cytotoxicity, complement-mediated cytotoxicity and phagocytosis of cancer cells coated with MAbs by reticuloendothelial system.
The patients suffering from leukemia, colorectal cancer, lymphoma and melanoma have been treated with MAbs. However, there was a wide variation in the success rate. A monoclonal antibody specific to the cells of leukemia is used to destroy the residual leukemia cells without affecting other cells. Abzyymes MAbs produced in mice and directly used for therapeutic purposes may appplications to the development of anti-mouse antibodies and hypersensitivity reactions.
All the cancer cells may not carry the same antigen for which MAb has been produced. Thus, MAbs may not be attached to some cancer cells at all. The free antigens of target cells present in the circulation may bind to MAbs and prevent them from their action on the target cells. In recent years, MAbs specific to T-lymphocyte surface antigens are being used for this purpose.
Food and Drug Administration for use as immunosuppressive agent after organ transplantation in humans. OKT 3 specifically directed against CD 3 antigen of T-lymphocytes is successfully used in renal and bone marrow transplantations. In the normal anzymes, CD 3 antigen activates T-lymphocytes and plays a key role in organ transplant rejection destroys the foreign cells in the host. This is prevented by use of MAb against CD 3 antigen.
Immunosuppression is the hall zbzymes of AIDS. This is caused by reduction in CD 4 cluster determinant antigen 4 cells of T-lymphocytes. The human immunodeficiency virus HIV binds to specific receptors on CD 4 cells by using surface membrane glycoprotein gp Genetic engineers have been successful to attach Fc portion of mouse abzymfs antibody to human CD 4 molecule.
Abzynes complex has high affinity to bind to membrane glycoprotein gp of virus infected cells. Autoimmune diseases like rheumatoid applicatiobs and multiple sclerosis are of great concern.
Some success has been reported in the clinical trials of rheumatoid arthritis patients by using MAbs directed against T-lymphocytes and B-lymphocytes. Toxins, drugs, radioisotopes etc. This allows higher concentration of drugs to reach the desired site with minimal toxicity. In this way, MAbs are used for the appropriate delivery of drugs or isotopes. The toxins can abzymss coupled with MAbs to form immunotoxins and used in therapy e.
This immunotoxin can be used to destroy the malignant T-cells in the patients suffering from T-cell leukemia Note: IL2-R is expressed in abnormal T-cells with lymphoid malignancies. Ricin abzhmes a cytotoxic protein derived from castor oil plant.
appliactions It is composed of two polypeptide chains A and B held together by a disulfide linkage. The B-chain of ricin binds to the cell surface. This binding facilitates the A-chain of ricin to enter the cell and inhibit the function of ribosomes i. This results in the death of cells Fig. Ricin can be subjected to oxidation to separate to Applicxtions and B chains. The toxic A-chain can be conjugated to MAb that is specific to cancer cells.
The tumor- specific MAb bound to A-chain of ricin binds to cancer cells and not to normal cells. Once the A-chain enters the cells, it blocks ribosomal function, leading to the death of cancer cells Fig. In general, the drugs are less effective in vivo in the living body when compared to in vitro in laboratory when tested with cultured cells. This is mainly due to the fact that sufficient quantity of the drug does not reach the target tissue.
This problem can be -solved by using tissue-specific MAbs. The drugs can be coupled with MAb directed against a cell surface antigen of the cells, say a tumor and specifically targeted to reach the site of action Fig.
In the treatment of certain diseases, a pro-drug an inactive form of the drug can be used.
This can be enzymatically converted to active drug in the target tissues.