Applications of Antibodies

Therapeutic applications of antibody-toxin conjugates may be limited because (1) antibody-toxin conjugates distribute nonspecifically to organs such as the liver and cause severe toxicity, (2) the bacterial toxin is immunogenic to humans, (3) tumor-associated antigens are often found in normal tissue (although levels are low), and (4) premature release of toxin from the antibody conjugate leads to systemic toxicity. 

The most predominant application of antibodies has been in the area of diagnostic assays, known as immunoassays, which exploits the specific interaction between the antibody and antigen. The world immunoassay market for clinical and food diagnostics, environmental analysis and other applications exceeded 1.2 billion in 1990. ELISA (Enzyme-Linked Immunosorbant Assay) represents 60% of that market (2). Annual growth rates have been projected at 10-15%. The food diagnostics is projected to grow to 500 million by the year 2000 (3). 

The therapeutic application of antibodies of non-human origin may cause problems because murine mAbs are recognized by the human immune system as extrinsic substances. In general, the first administration of 100% murine mAbs is well tolerated. However, it can induce the production of specific anti-antibodies by the human body, the so-called human anti-murine antibodies (HAMAs), against the murine mAbs. Repeated administration of 100% murine mAbs may cause an immune response with influenza-like symptoms and even severe states of shock. 

Another application of antibodies is to treat autoimmune diseases, which occur due to a deficiency of the immune system that recognizes an endogenous molecule as a foreign element. The most common immu-notherapeutic approach in these cases is that the antibody is directed against the antigen on the surface of the lymphocytes responsible for the immune response. 

Haab BB. Methods and applications of antibody microarrays in cancer research. Proteomics 2003 3(11) 2116-2122. Review. 

Because of the superior morphology provided by formalin-fixed paraffin-embedded tissues, this has become the medium of choice for most clinical and research studies. The peroxidase-labeled antibody method, introduced in 1968, was the first practical application of antibodies to paraffin-embedded tissues and overcame some of the limitations of earlier fluorescence antibody methods (1). These pioneering studies using enzyme labels instead of fluorescent dyes opened the door to the development of modern methods of immuohistochemistry. 

The successful application of antibody tagged particles as markers for antigens on the surface of red blood cells and lymphocytes. 

The application of antibodies in cardiovascular targeting in vivo originated with the experimental demonstration of the feasibility of using radiolabeled antimyosin antibody for diagnosis of acute myocardial infarction in 1976. Since then, the use of antibodies in the cardiovascular system has encompassed imaging of myocarditis,heart transplant rejection, dilated cardiomyopathy, alcohol induced cardiomyopathy,adriamycin cardiotoxicity, various other cardiomyopathies, vascular clots, atherosclerotic lesions,and even certain cancers such as soft tissue sarcomas.f Yet the best characterized and studied antibody for cardiovascular diagnostic targeting is monoclonal antimyosin Fab for its exquisite specificity... 

Antibody-directed drug delivery has firmly established its remarkable value in the marketplace in recent years. In addition to several drugs that are already approved by the FDA, many more drug candidates are in the development pipeline. Although initial clinical indications for this class of therapeutic molecules are limited to oncology, much broader applications of antibody drug delivery are anticipated in the future, as the improved specificity and potency offered by this approach continues to be highly desirable in many therapeutic areas. 

Excess buffer or nonimmune serum allowed to remain on specimen Remove excess buffer before application of antibodies. 

To date, monoclonal antibodies or lectins specific for almost eveiy cell-type of the nephron and collecting (duct) system are available (Figure 2). This array of monoclonals/lectins represents a powerful tool for the immunoselection of individual cell-types. However, the applicability of antibodies and lectins for immunoselection is limited by the membrane expression density of the antigens/oligosaccharide moieties sought, their stability and affinity. 

Taylor R F 1990 Development and application of antibody- and receptor-based... 

The exquisite dereplication ability of the mammalian immune systems to identify and remove unwanted xenobiotics has been utilized by some natural products chemists. Application of antibody-based detection methods for natural products have thus far been limited to those natural products that are of significant economic interest, either as agricultural contaminants or as potential pharmaceutical constituents. However, the development of more readily available microbially derived antibody fragments (58) and the advent of various methods for increasing their affinity (59) augur well for more widespread use of these technologies for dereplication in the future. Of the numerous reports of the use of this technique of antibody-based detection to identify natural products and related family members, two representative examples follow. 

Number of publications cover the topic of the application of antibodies as capture and/or detection reagents in high-throughput analyses of protein abundance (3,4,5,6,7,8,9,10,11). 

Takasaki, W. Tanaka, Y. Application of antibody-mediated extraction for the stereoselective determination of the active metabolite of loxoprofen in human and rat plasma. Chirality 1992, 4, 308-315. 

As antibody catalysis has progressed one catalytic antibody, 38C2, became commercially available, with much attention being drawn to its practical application in organic synthesis. In fact, there are many publications reviewing applications of antibody catalysis in asymmet-... 

Antibodies represent a powerful tool for specific detection and enrichment of posttranslationally modified proteins from different sources, including cell lysates. Only recently, the production and possible applications of antibodies... 

The methods addressed in this chapter are specifically concerned with the generation and application of antibodies that recognize adducts in polymeric DNA. 

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