Set up and optimization of a fermentation protocol for the production of a human antibody fragment (Fab') express in E. coli. Pre-pilot and cGMP pilot scale studies

can be the ther-apeutic of choice for solid tumors due to shorter circulat-ing half life and a higher tumor penetration, bothcharacteristics well suited in a radio immunotherapy(RIT) approach.Ovarian cancer is the leading cause of death among gyne-cological tumors. Standard first line therapy consists ofsurgery followed by chemotherapy cycles. About 90% ofpatients relapse with a 5-year survival rate of 5–20% [1].So far, second line chemotherapy after clinical relapse hasshown limited efficacy. With the advancement of therecombinant biotechnology, a novel approach based onhuman monoclonal antibody immunotherapy has beganto be investigated. The alfa folate receptor ( αFR), which isa 38000 Dalton anchored membrane protein, is overexpressed in more than 90% of ovarian carcinoma cells,and in 60% of other gynecological carcinomas [2]. In con-trast to normal epithelial cells, ovarian carcinoma cellsexpress this receptor on their external surface making itaccessible for binding to monoclonal antibodies.The basic concept of our project is to produce a fullhuman F(ab')