EGFR Peptides as Vaccines in Anti-Tumor Immunity

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$1,118,129.00
Award Year:
2010
Program:
STTR
Phase:
Phase II
Contract:
2R42CA128165-02A1
Award Id:
n/a
Agency Tracking Number:
R42CA128165
Solicitation Year:
2010
Solicitation Topic Code:
NCI
Solicitation Number:
PA09-081
Small Business Information
BOX 8175, NEW HAVEN, CT, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
142406110
Principal Investigator:
MARK MAMULA
(203) 737-2840
mark.mamula@yale.edu
Business Contact:
MARTIN MATTESSICH
(203) 393-9439
mmattessich@L2dx.com
Research Institute:
Yale University

47 COLLEGE STREET, STE 203
NEW HAVEN, CT, 06520-8047
() -
Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Epidermal Growth Factor Receptor (EGFR) bearing tumors remain as one of the most insidious and difficult to treat human malignancies, affecting thousands of individuals each year. Our proposed studies are aimed at developing novel tumor immunotherapy by using both cryptic peptides of EGFR protein as well as isoaspartyl modified EGFR peptides, both of which break immune tolerance to self tumor antigens expressed on EGFR positive 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. Previous studies demonstrate that vaccination with xenogenic peptide antigens can overcome immune tolerance. Ourphase I studies have demonstrated the ability of peptide vaccination to elicit anti-EGFR antibodies in a manner that resembles binding of tumor cells by Erbitux, a commercial monoclonal antibody currently used in the immunotherapy of human colon cancer. Similar to EGFR binding by Erbitux, peptide vaccination generated antibody that binds native EGFR protein on living tumor cells and in solid phase immunoassays. We have demonstrated that immunization with EGFR peptides elicits antibodies that inhibit tumorgrowth in vitro and control tumor growth in vivo. The goals of the Phase II study are to develop enhanced anti-EGFR tumor immunity with a select group of EGFR peptides in combination with novel TLR-based adjuvants. We will also examine the therapeutic synergy in our peptide-based vaccination strategy with HER2 based immunotherapeutics. In support of our own approaches, recent studies have demonstrated that many tumor types co-express EGFR as well as HER2 protein. It is the goal of the Phase II studies to match the ideal peptide based immunizations in combination with TLR adjuvant and monoclonal antibody therapy to develop long term immunity and tumor clearance in murine models of human EGFR cancers. PUBLIC HEALTH RELEVANCE: Epidermal Growth Factor Receptor (EGFR) protein is the tumor target of approved monoclonal antibody therapies. This project will develop a candidate cancer vaccine to treat patients with aggressive tumors that express this protein. The cancer vaccine would be used in combination with existing therapies to improve long-term responses to cancer therapy.

* information listed above is at the time of submission.

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