NOVEL TECHNOLOGIES FOR HEPATOMA GENE THERAPY

We propose a novel method for the rapid, large scale, low cost production of recombinant tumor-reactive humanized monoclonal antibodies in the milk of cows. We will express in milk commercially useful quantities of a single chain monoclonal antibody following gene delivery in vivo to effect a transomatic modification of the mammary epithelium of cattle, using a pseudotyped, replication defective, retroviral vector. We will collect milk and evaluate functionality of the single chain antibody. The cc49 chimeric single chain antibody reacts with the TAG-72 antigen present on a wide range of human carcinomas, including colorectal, gastric, pancreatic, mammary, ovarian, and endometrial carcinomas and adenocarcinomas of the lung but is absent on most normal human tissues. The fact that the cc49 antibody reacts with most carcinomas, yet demonstrates little reactivity to most normal tissues, makes it an attractive diagnostic and therapeutic agent. We anticipate that the potential annual need for this antibody in the U.S. alone, if further proven effective in clinical trials, approximates 150kg of purified antibody, capable of treating 150,000 patients. This quantity is currently beyond the financial or reagent production capabilities of more traditional bioreactor systems but well within the scope of production in a bovine milk source.