Monoclonal antibody specificity: Orthoclone OKT3 T-cell blocker.

Abstract

Orthoclone OKT3, a murine monoclonal antibody of the IgG2a class, was initially developed as a pan-T cell monoclonal antibody for use as a marker to differentiate between cell subsets. Only later did its potential role in treating allograft rejection become apparent. At first, its mechanism of action in such cases was not understood. Subsequent investigations demonstrated that OKT3 not only removed all T cells, but also specifically interacted with the T3 antigen recognition complex found on late thymocytes and mature T cells, consequently blocking the immunologic function of these cells. When injected into a patient, OKT3 can act in three ways to reverse allograft rejection. It initially coats, or opsonizes, the circulating T cells, which are then removed by the reticuloendothelial cells in the liver and spleen. OKT3 also modulates the T3 antigen recognition complex of circulating T cells, producing cells with all their phenotypic characteristics, except for the T3 molecules and the antigen recognition complex. The key mechanism of action of OKT3 in treating allograft rejection may be its ability to block the killer function of sessile T cells. In contrast to polyclonal antiserums, each molecule of OKT3 monoclonal antibody is virtually identical and has an identical specificity, thereby producing consistent reactivity to human T cells with a defined and relatively low degree of toxicity. Although derived from a hybridoma and grown in mouse ascites, OKT3 undergoes numerous purification steps to ensure that the final product is sterile, biochemically pure, homogeneous IgG2a. Furthermore, each batch is checked to make sure that its functional activity is the same as the standard.(ABSTRACT TRUNCATED AT 250 WORDS)