TARGETED THERAPY FOR ADULT T-CELL LEUKEMIA

THIS PROJECT IS DESIGNED TO TEST THE FEASIBILITY OF TARGETED THERAPY FOR ADULT T-CELL LEUKEMIA (ATL) USING A NOVEL CD4 RECEPTOR-SELECTIVE DELIVERY SYSTEM BASED ON "VIRALMIMICRY": ARTIFICIAL VIRAL ENVELOPES CONTAINING RECOMBINANT GP160, OR COVALENTLY COUPLED RECOMBINANT GP120, OF THE HUMAN IMMUNODEFICIENCY VIRUS (HIV). ATL IS AGGRESSIVE, RESISTANT TO CURRENTLY USED TREATMENT MODALITIES, RESULTING IN AN EXTREMELY POOR PROGNOSIS (SURVIVAL <6 MONTHS) EVEN WITH THE MOST AGGRESSIVE CHEMOTHERPAY. A MAJORITY OF ATL CELLS EXPRESSES THE CD4 RECEPTOR RENDERING THEM A "NATURAL" TARGET FOR CD4-TOPIC CARRIER SYSTEMS. WE HAVE DESIGNED ARTIFICAL HIV ENVELOPES THAT MIMIC THE NATURAL VIRUS BOTH PHYSICALLY AND FUNCTIONALLY, PROVIDING A MEANS TO TARGET IMMUNOTOXINS AND GENETIC CONSTRUCTS (E.G. ANTI-SENSE DNA) TO ATL CELLS. THE SPECIFIC AIMS OF PHASE I ENTAIL (i) DEMONSTRATING SELECTIVE DELIVERY TO ATL CELLS, (ii) EXAMINING THE ABILITY OF ENVELOPE-INCORPORATED CELL TOXIN RICIN-A TO SELECTIVELY KILL ATL CELLS, (iii) TESTING THE ABILITY OF ENVELOPES TO DELIVER GENETIC MATERIAL TO AND EXPRESS GENETIC INFORMATION IN ATL CELLS. DEMONSTRATION OF THE FEASIBILITY OF CANCER TARGETING USING THIS APPROACH WOULD RENDER ATL A POTENTIALLY CURABLE DISEASE, AND WOULD HAVE A MULTIPLIER EFFECT ON MANY OTHER THERAPEUTIC STRATEGIES INCLUDING ANTIMICROBIAL, GENE AND IMMUNOTHERAPY.