IMMUNOTOXIN THERAPY FOR AIDS

THE GEOMETRIC INCREASE IN THE NUMBER OF INDIVIDUALS INFECTED BY HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) HAS CREATED SERIOUS SOCIAL, ECONOMIC, AND LIFE-THREATENING ISSUES FOR THE HUMAN RACE. IT IS OF PRESSING CONCERN TO DEVELOP EFFECTIVE MEASURES FOR CONTROLLING THE SPREAD OF THIS DISEASE. THIS RESEARCH SEEKS TO DEVELOP A SPECIFIC IMMUNOTOXIN BY CHEMICALLY COUPLING A TOXIN TO A GROUP-SPECIFIC NEUTRALIZATION MONOCLONAL ANTIBODY. IN ADDITION TO ITS RETAINED ABILITY TO NEUTRALIZE FREE VIRIONS, THIS IMMUNOTOXIN CAN SPECIFICALLY KILL HIV-1 INFECTED CELLS AT LOW CONCENTRATIONS. THIS CYTOTOXIC PROPERTY WILL MEDIATE THE ELIMINATION OF LATENTLY INFECTED CELLS IN INFECTED INDIVIDUALS. THE SPECIFIC AIMS OF THIS PHASE I PROJECT ARE TO: (1) CONSTRUCT IMMUNOTOXINS BY COUPLING POKEWEED ANTIVIRAL PROTEIN TO GROUP-SPECIFIC NEUTRALIZING MONOCLONAL ANTIBODIES; (2) DETERMINE THE ABILITY OF THESE IMMUNOTOXINS TO PREVENT VIRAL INFECTION AND REPLICATION AFTER BINDING TO FREE VIRIONS, AND TO BLOCK SYNCYTIUM FORMATION BETWEEN INFECTED CELLS AND CD4-POSITIVE CELLS; AND (3) EXAMINE THE ABILITY OF THE IMMUNOTOXIN TO KILL HIV-1 INFECTED CELLS EXPRESSING GP120 ON THE CELL SURFACE. THE LONG-TERM OBJECTIVE OF THE PROJECT IS TO DEVELOP A PANEL OF SPECIFIC AND EFFECTIVE IMMUNOTOXINS AS THERAPEUTIC AGENTS FOR AIDS.