The general aim of this project is to determine the chemical interactions which occur at the surfaces of cells which affect cellular differentiation and organization. Specifically we have studied one type of interaction, plasma membrane receptor mediated entry of proteins into the cell cytosol. These studies have been done by developing techniques to construct artificial protein conjugates containing the active fragment of a toxin and another receptor specific binding protein. Such artificial protein conjugates have value as a new class of pharmacologic reagents. Monoclonal antibody ricin conjugates or immunotoxins directed against human T cells effectively deplete these cells from donor bone marrow permitting bone marrow transplants apparently free from moderate to severe forms of graft versus host disease. This will provide a new treatment for leukemia, aplastic anemia and autoimmune diseases such as multiple sclerosis, Guillain Barre Syndrome, systemic lupus erythematosus and perhaps other diseases of the immune system such as acquired immunodeficiency syndrome. In addition, these reagents are useful for enzyme replacement therapy and in organ transplantation.
