Preparation, characterization, and primate testing of monoclonal antithymocyte globulin.

Abstract

Monoclonal antibodies specific for T cells from both the human and rhesus primate species were detected by their ability to inhibit T cell rosette formation with sheep erythrocytes. The antibodies were shown by fluorescence techniques to react with all thymocytes and peripheral blood T cells but not to B cells, monocytes, platelets, or erythrocytes. Rosette inhibition titers of these antibodies were 30-fold lower when rhesus, rather than human T, cells were used as the rosette-forming cell in assay. Nonetheless, two monoclonal antibodies, of the IgG3 isotype, termed antithymocyte monoclonal (ATM) e.1 and 2.2, were shown to depress selectively circulating T cells to nondetectable levels following single dose administration to rhesus primates and to prolong skin allograft survival in a rhesus primate given a 6-dose course of treatment. The rhesus primates suffered no ill effects and no peripheral blood cellular component other than T cells was depressed. Monoclonal antibody secreting hybridoma cells are capable of producing ATM 3.1 and 3.2 in quantity when grown as peritoneal tumors in selected mouse hybrids. Purification of ATM 3.1 or 3.2 is easily accomplished by affinity chromatography on protein A. These properties suggest that ATM antibodies may become useful immunosuppressive agents in clinical transplantation.