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Abstract
Grant Number: 1R43CA096169-01A1 PI Name: HUMPHREYS, ROBERT E. PI Email: antigenexp@aol.com PI Title: ASSOCIATE PROFESSOR Project Title: HER-2/neu T Helper/Memory Vaccine for Breast Cancer Abstract: DESCRIPTION (provided by applicant): Antigen Express scientists have demonstrated that the li-Key segment of the li protein, acting at an allosteric site of Class II molecules, facilitates charging by suitable vaccine peptides at the antigenic peptide-binding site. The potency is enhanced (>250) times when the N-terminus of the antigenic peptide is linked to the li-Key peptide (li-key/antigenic epitope hybrid). Such hybrids composed of the Her-2/neu (777-789) epitope are much more potent in stimulating T lymphocytes of patients with metastatic breast carcinoma as measured by IFN-gamma release. In order to develop anti-Her-2/neu immunotherapies, we will: 1) design 9 li-Key/Her-2/neu hybrids using peptides predicted (or previously demonstrated experimentally) to act as good MHC class II epitopes and test their activity in vivo; 2) design and test in vivo a double hybrid composed of the most potent li-Key/Her-2/neu hybrid further linked to an experimentally proven CTL epitope; and 3) characterize the efficacy of our most potent double hybrid in a murine tumor model. We expect a robust augmentation of CTL activity to be obtained through enhanced Th memory/activity by li-Key. These studies address key questions to justify clinical trials with li-Key/HER-2neu antigenic epitope hybrids peptide vaccines in the treatment of breast cancer.
Thesaurus Terms:
MHC class II antigen, breast neoplasm, helper T lymphocyte, immunologic memory, neoplasm /cancer vaccine, protein engineering, protooncogene, vaccine development
invariant chain, neoplasm /cancer immunotherapy
laboratory mouse, peptide chemical synthesis
Institution: ANTIGEN EXPRESS, INC. 100 BARBER AVE WORCESTER, MA 01606 Fiscal Year: 2003 Department: Project Start: 21-JAN-2003 Project End: 31-DEC-2003 ICD: NATIONAL CANCER INSTITUTE IRG: ZRG1