Therapeutic application of monoclonal antibodies

The transformation of a cell to the cancerous state is normally associated with increased surface expression of antigens recognized as foreign by the host immune system. These surface antigens, often termed tumour antigens or tumour surface antigens, are either not expressed at all by the untransformed cell or are expressed at such low levels that they fail to induce immunological tolerance. 

The presence of tumour-specific antigens implies that the immune system should be capable of recognizing and destroying transformed cells. This concept, known as immunosurveillance, probably does function to some extent in the body. The immune system does respond to the presence of some tumours, causing their partial or complete regression. The major anti-tumour immune elements include  

CEA-Scan (Arcitumomab, murine Mab fragment (Fab), directed against human CEA) 

MyoScint (Imiciromab-Pentetate, murine Mab fragment directed against human cardiac myosin) 

OncoScint CR/OV (Satumomab Pendetide, murine Mab directed against TAG-72, a high molecular weight tumour associated glycoprotein) 

Diagnostic imaging (e.g. of cancer, infectious diseases, cardiovascular disease and deep vein thrombosis) 

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Berger, M., Shankar, V., and Vafai, A. 2002. Therapeutic applications of monoclonal antibodies. American Journal of the Medical Sciences 324(1), 14-30. 

Lally, E.V. (1991). Therapeutic application of monoclonal antibodies in the rheumatic diseases. In Monoclonal Antibodies, Cytokines, and Arthritis. T.F.Kresina, ed. (New York Marcel Dekker), pp. 37 56. 

The following discussion is focused on in vitro applications of monoclonal antibodies and nucleic acid probes as diagnostic reagents. The principles of production and characteristics of Mabs are described in Chapter 2. Their use as in vivo diagnostic imaging agents has been discussed in Chapter 3 in the context of therapeutic applications, and is not discussed further here. The principles of PCR and nucleic acid hybridization have been discussed in Chapter 2 and Chapter 4, respectively. 

Numerous investigators have reported and reviewed the chnical application of monoclonal antibodies in various areas, including organ transplantation, neoplastic diseases, severe sepsis, and chronic inflammatory diseases. Collectively, these antibodies generally did not produce major adverse effects. The rapid development of antibodies against murine monoclonal antibodies is one of the most important clinical hmitations to their therapeutic use, but the development of humanized (chimeric human/ murine) monoclonal antibodies has improved their safety. Monoclonal antibodies have also been used in non-immune mediated diseases, such as cancer, septic shock, reperfusion, and as antiplatelet drugs. Treatment of neoplastic diseases with monoclonal antibodies is theoretically attractive. Unfortunately none of the monoclonal antibodies available at present has been demonstrated to be strictly tumor-specific, and binding of antibody to normal cells has been shown to be the major unknown factor for toxicity (6). 

Monoclonal antibodies offer some of the greatest promise and pitfalls in medicine. To provide researchers and clinicians with a greater understanding of this class of therapeutics, this chapter will review the history, production, structure, function, toxicities, and clinical applications of monoclonal antibodies in oncology. 

Immunoglobulins in the form of monoclonal antibodies are manufactured commercially for therapeutic and diagnostic uses. Major areas of consideration in these applications are quality control and bioactivity. Separation of immunoglobulins has proven to be a challenge even for well-established techniques such as HPLC. Difficulties arise due to the large size of antibodies and their surface properties, which increase their tendency to interact with proteins and matrix. 

With the broadening of the therapeutic applications of biopharmaceuticals, new safety issues can be anticipated in the future. Since the late nineties, ritux-imab (anti-CD20 monoclonal antibody) has been used to treat non-Hodgkin s... 

Ribatti, D. (2014) From the discovery of monoclonal antibodies to their therapeutic application an historical reappraisal. Immunol Lett, 161 (1), 96-99. 

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