Immunotoxins are selective cytotoxic agents, produced by the covalent linkage of a generalized eukaryotic toxin to a cell-type specific antibody. Unlike traditional antibiotics, which work because of metabolic differences between host and infective organism, the immunotoxins exploit cell surface antigenic differences for their effectiveness. Consequently, immunotoxins have potential as therapeutic agents for the treatment of diseases, such as neoplastic and parasitic disease, which are presently difficult to treat. Evidence obtained with a model protozoan indicates that the construction of practical immunotoxins for this type of organism may be possible. Further, five catalytic inhibitors of protozoan ribosomes have been identified by screening most of the known catalytic toxins. One major question that must be answered is: Do protozoans possess cell surface antigens and internalization pathways appropriate for the employment of presently known catalytic toxins? The research proposed here is designed to answer that question by preparing immunotoxins that react with essentially all Acanthamoeba castellanii cell surface antigens, and evaluating them for cell killing potential. In addition to determining the two most important criteria of an effective trophozoite immunotoxin, target antigen and toxin, the proposed research will also determine effective antibody valency, and begin the process of preparing a cyst immunotoxin. Should the criteria for an effective protozoan immunotoxin be developed quickly, research on an immunotoxin for a related human pathogen, and in vivo studies will be initiated.
| Yang, S; Villemez, C (1994) Cell surface control of differentiation in Acanthamoeba. J Cell Biochem 56:592-6 |
