The goal of Dr. Wei's research is to prevent breast cancer progression by immunotherapy. Recombinant erbB-2 DNA vaccines and therapeutic pro-peptides are being developed to activate anti-tumor immunity. ErbB-2 is over-expressed by several types of solid tumors including breast cancer and is recognized by the immune system as a tumor associated antigen. Native ErbB-2 is a transmembrane tyrosine kinase which mediates oncogenic activity. A panel of recombinant vaccines have been generated. The kinase activity is eliminated by replacing ATP binding lysine residue 753 with alanine, resulting in a mutant ErbB-2 which exerts anti-kinase activity. Modification of the extracellular domain further changes the processing and presentation of ErbB-2 antigen. A cytoplasmic form of ErbB-2 was generated by deleting the signal peptide for ER translocation and this mutant ErbB-2 induces anti-tumor immunity without antibody response. Mutant ERBB-2 vaccines in various forms are being tested and compared.

In the pro-peptide study, we are testing the hypothesis that breast cancer can be eliminated by immunizing the patients with defined foreign peptides and by delivering to the lesions therapeutic peptides in microparticles or as pro-peptides. The test peptides will be LacZ p876 presented by Ld, influenza matrix protein p58 presented by HLA-A2.1 and Pan DR Reactive Epitope (PADRE) which can be presented by more than 10 different human and mouse class II major histocompatibility complex (MHC). The pro-peptides are generated by conjugating side groups to the peptides through a spacer. Pro-peptides are inert because they lose the binding motif to MHC. Active peptides are released from the pro-peptides by specific enzymes secreted at the tumor sites to mark the tumor for immune destruction. The reagents developed in both studies will be candidate breast cancer therapeutics for patients.