CRADA Final Report: ErbB2 Targeted Cancer Therapeutics

The aim of the study was to design novel therapeutic strategies for the treatment of carcinomas which overexpress the erbB-2 oncogene product and/or the activator (HRG). erbB-2 is a tyrosine kinase growth factor receptor, that overexpression of which in invasive breast, prostate, ovarian and lung carcinomas correlates with poor prognosis and poor overall survival. In breast carcinomas, erbB-2 is overexpressed in 25%-30% of the invasive phenotype and in 70% of ductal carcinomas in situ. On the other hand, the erbB-2 activator, heregulin (HRG) is expressed in about 30% of invasive breast carcinomas and it is highly expressed in other carcinoIl1as including, ovarian, lung, and prostate. Interestingly, only 6% of invasive breast carcinomas co-express both HRG and erbB-2. It is known today that tumors that overexpress erbB-2 are a leading cause of death, making erbB-2 and its activator HRG critical targets for therapy. Targeting both the receptors and the activator would be beneficial for a significant number of cancer patients. At the final stages of the project we had obtained significant improvements over the peptide quality but not significant improvements were made towards the generation of humanized monoclonal antibodies.