Monoclonal antibodies in diagnostics

Wick MR. Antibodies to desmin in diagnostic pathology. In Wick MR, Siegal GP, eds. Monoclonal antibodies in diagnostic immunohistochemistry. New York Marcel Dekker 1988 93-114. 

Khoudi, FI., Laberge, S., Ferello, J.M., Bazin, R., Darveau, A., Castonguay, Y., Allard, G., Lemieux, R., and Vezina, L.R (1999). Production of a diagnostic monoclonal antibody in perennial alfalfa plants. Biotechnol. Bioeng. 64 135-143. 

Animal cells, and in particular mammalian cells, are cultured on industrial scale to produce vaccines, interferons, and monoclonal antibodies for diagnostic and therapeutic uses, among others materials. 

The first assay (a radioimmunoassay) that measured cTnl used polyclonal anti-cTnl antibodies. The first monoclonal enzyme-linked immunosorbent assay, anti-cTnl antibody-based immunoassay, was described by Bodor and co-workers (1992). Numerous manufacturers have now developed monoclonal antibody-based diagnostic immunoassays for the measurement of cTnl in serum. Assay times range from 5 to 30 minutes. 

Compared with the therapeutic use of human monoclonal antibodies, the use of rodent (mouse or rat) monoclonal antibodies in vivo is disadvantageous because the xenogeneic antibody can induce immune responses that will mitigate the effectiveness of the antibody and/or cause adverse reactions in the recipient. Thus, the authors of one report concluded that antimouse immunoglobulin responses in human patients have limited the usefulness of murine monoclonal antibodies in more than half of those treated (12). The formation of human antimouse antibodies has been described both when murine monoclonal antibodies are used as a diagnostic tool in vivo and when they are used therapeutically (13-16). 

Cummins and co-workers were the first to develop a radioimmunoassay to measure cTnl that used polyclonal anti-cTnl antibodies. Although the assay showed approximately 2% cross-reactivity with skeletal Tnl, it stiU had excellent clinical specificity for cardiac muscle injury. The assay was never automated or developed for commercial use. The first monoclonal ELISA, anti-cTnl antibody-based immunoassay, was described by Bodor et al. This assay has less than 0.1% cross-reactivity with skeletal Tnl, but it was not suited for clinical use because of the lengthy assay time. Over the past 15 years, numerous manufacturers have described the development of monoclonal antibody-based diagnostic immunoassays for the measurement of cTnl in serum. Assay times range from 5 to 30 minutes. As shown in Table 44-1, over a dozen assays have been approved by the FDA for patient testing within the United States on central laboratory and POCT platforms. In addition to these quan-... 

Various heteroantisera and monoclonal antibodies to OCN have been used in reported immunohisto-chemical studies, " which indicate that polyclonal anti-OCN reagents are inferior to monoclonal antibodies for diagnostic work because of problems with specificity. Although studies have shown that OCN has a reasonable level of sensitivity for osteoblastic differentiation (approximately 70%) and is, for practical purposes, apparently virtually completely specific for bone-forming cells, 740 rarely used in clinical practice. 

Khoudi, H., et al.. Production of a diagnostic monoclonal antibody in perennial alfalfa plants. Biotechnol Bioeng, 1999 64(2) 135-143. 

S. L. 1986. Detection of Pythium blight in turfgrass using monoclonal antibody-based diagnostic test (abstr,). Phytopathology. press)... 

Table 1 FDA approved diagnostic imaging monoclonal antibodies in oncology... 

Monoclonal antibodies (mAh) are molecules that recognize and bind a specific foreign substance called an antigen. They are produced from a single clone of B lymphocytes. Conventionally, mouse mAh have been generated for experimental and diagnostic use. Techniques have been developed to humanize mouse mAh to facilitate their therapeutic use in humans. It is also now possible to make mAh which are fully human. 

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