Version 2.5.2.0

Abstract

Grant Number:	5R42CA106107-03
Project Title:	Modified HER-2 Tumor Antigens for Vaccination in Cancer

PI Information:	Name	Email	Title
	MAMULA, MARK J.	mark.mamula@yale.edu	ASSOCIATE PROFESSOR

Abstract: DESCRIPTION (provided by applicant): Breast cancer remains 1 of the most insidious and difficult to treat human malignancies, affecting thousands of individuals each year. Our proposed studies are aimed at developing a novel tumor immunotherapy by using cryptic peptides of Her-2 protein and modified Her-2 peptides, both of which break immune tolerance to "self " tumor antigens expressed on breast cancer cells. In general, most tumor antigens have been characterized as normal, non-mutated self peptides, linking the concepts of autoimmunity with the development of tumor immunity. Our phase I studies have demonstrated the ability of peptide vaccination to elicit anti-Her-2 antibodies that resemble Herceptin, a monoclonal antibody currently approved for immunotherapy of human breast cancer. Similar to Her-2 binding by Herceptin, antibodies induced by peptide vaccination bind native Her-2 protein on living tumor cells and in solid phase immunoassays, as well as denatured Her-2 protein and peptides therein. We have demonstrated that immunization with Her-2 peptides elicits antibodies that inhibit tumor cell growth in vitro and in vivo. The goal of the Phase II study is to develop enhanced anti-Her-2 tumor immunity with a select group of Her-2 peptides in combination with adjuvants approved for human use, alum and novel TLR-based adjuvants. At present, antibody-mediated treatment of breast cancer requires prolonged administration of the therapeutic. This work will attempt to establish vaccine- based long term immunity with antibody specificities and biologic efficacy comparable to Herceptin therapy. The overall objective of this research is to develop peptide-based vaccination strategies to mimic the anti-tumor properties of Herceptin, an antibody with proven clinical efficacy in patients with breast cancer.

Thesaurus Terms:

There are no thesaurus terms on file for this project.

Institution:	L2 DIAGNOSTICS, LLC
	NEW HAVEN, CT 06530
Fiscal Year:	2007
Department:
Project Start:	01-MAR-2004
Project End:	31-AUG-2008
ICD:	NATIONAL CANCER INSTITUTE
IRG:	ZRG1

---