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) test tumor rejection with peptide therapy. The 3-D tumor growth inhibition assay is established. D2F2 mammary tumor and another tumor line 168 with metastatic potential were inhibited by CTL in the 3-D matrix. HLA-A2.l associated Flu peptide MP-58 GILGFVFTL was used for pro-peptide development. Pro-peptide was synthesized with a minimal protection approach. Purification of the pro-peptide to high purity is the current goal. To test therapeutic effect, mice were immunized with MHC Ip876 and MHC II PADRE, injected with peptide loaded tumor cells, followed by local peptide injections. Complete tumor rejection was achieved. Challenging tumor cells not pre-coated with peptide were not rejected by p876 treatment. Vaccination and therapy with PADRE alone demonstrated anti-tumor effect and this activity is being further pursued. If MRC I peptide can be delivered directly unto tumor cells in the form of pro-peptide, combined treatment with PADRE may exert enhanced efficacy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385378
Entities
People
- Wei Wei-zan
Organizations
- Wayne State University