Development of Pro-Peptide Immunotherapy for Breast Cancer
Annual rept. 1 Jul 2000-30 Jun 2001
WAYNE STATE UNIV DETROIT MI
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This study tests whether breast cancer can be eliminated by immunization with foreign peptides followed by delivery of peptides to tumors. We proposed to 1 establish an in vitro assay to measure tumor growth inhibition, 2 synthesize pro-peptides for activation at the tumor site by beta-glucuronidase, and 3 test tumor rejection with peptide therapy. In this funding year, Flu MP58 pro-peptide was synthesized, purified to 76 purity with preparative HPLC and was suitable for HLA binding analysis. MP58 peptide bound to human HLA-A2.1 cells in a dose dependent manner in the range of 15 to 60 mu-M. MP58 pro-peptide up to 120 mu-M did not bind to HLA-A2.1. In the presence of 200 or 300 unitml of beta-glucuronidase, A2.1 binding MP58 was released from the pro-peptide as demonstrated by its binding to HLA-A2.1. The synthesis and purification of MP58 pro-peptide demonstrated the chemical feasibility of pro-peptide development. The release of active peptide by beta-glucuronidase demonstrated the precise and controlled generation of an antigenic epitope from a stealth agent as predicted by our design. Pro-peptide is a new and novel agent with strong potential for cancer immunotherapy.
- Medicine and Medical Research