Development of Pro-Peptide Immunotherapy for Breast Cancer

摘要

The proposed study will test the hypothesis that solid tumors can be eliminated by immunizing the host with specific foreign peptides and by delivering these peptides to the tumors in the form of pro-peptides which are activated at the tumor sites. This immunotherapy approach takes advantage of the potent tumor destruction capacity of T cells and is independent of self tumor- antigens. The therapeutic peptides will be conjugated to glucuronide through a spacer to form pro-peptides which will have increased aqueous solubility and no longer bind the MHC. Glucuronidase liberated by the tumor cells and tumor infiltrating inflammatory cells is expected to convert the pro-peptides to the active, MHC binding peptides in the vicinity of the tumor mass. The potent peptide specific CTL in vivo are expected to kill the tumor cells or the stromal/endothelial cells surrounding the tumor bed when these cells are marked on their MHC by the liberated peptides, achieving the goal of immunotherapy with foreign peptides. The technical objectives are to (1) Establish an in vitro assay to measure tumor growth inhibition by peptide specific T cells and pro- peptides, (2) synthesize and test the activity of pro- peptides to be activated by beta-glucuronidase at the tumor site and (3) Develop human anti- MP58 CTL line and measure pro-peptide activity with anti-MP58 CTL.