A Conjugate of α-Amanitin and Monoclonal Immunoglobulin G to Thy 1.2 Antigen Is Selectively Toxic to T Lymphoma Cells

A covalent conjugate of an alpha-amanitin azo derivative and a monoclonal immunoglobulin G to the Thy 1.2 antigen on murine T lymphocytes was synthesized. The conjugate was 375- to 750-fold more inhibitory to murine T lymphoma S49.1 cells than the unconjugated derivative. At 0.7 X 10(-7) to 1.5 X 10(-7) M and at 4 X 10(-7) M amanitin equivalents, the conjugate inhibited protein synthesis in S49.1 cells by 50 percent and 80 to 96 percent, respectively. At these concentrations, mutant Thy l-deficient S49 cells and other murine lymphoma lacking Thy l altogether or carrying Thy 1.1 antigens were unaffected. This result demonstrated the potential for targeting amanitin to specific cell types.