Development of Pro-Peptide Immunotherapy for Breast Cancer
Abstract
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) develop human CTL line and measure pro-peptide activity with human CTL. We tested two methodologies for synthesizing Flu MP58 pro-peptide. Condensation of Beta-glucuronide conjugated glycine to octapeptide ILGFVFTL was superior when compared to direct conjugation of beta-glucuronide to the nonapeptide GILGFVFTL. A human CTL line to MP58 was established by repeated stimulation of CD8 T cells with MP58 loaded antigen presenting cells. MP58 loaded T2 cells were lysed by CTL at E:T ratio of 10:1 - 2:1. The same CTL did not lyse T2 cells loaded with pro-peptide beta-Glu-MP58 unless beta-glucuronidase was added to the culture, further demonstrating liberation of active MP58 from the prodrug to mark tumor cells for CTL lysis. These results demonstrate that peptide prodrugs can be converted by beta-glucuronidase to active peptide and mark tumor cells for CTL mediated lysis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408383
Entities
People
- Wei-Zen Wei
Organizations
- Wayne State University