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. Our phase 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 tumor growth 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
3R42CA128165-03S1
Application #
8647974
Study Section
Program Officer
Haim, Todd E
Project Start
2013-09-01
Project End
2014-06-30
Budget Start
2013-09-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$262,925
Indirect Cost
Name
L2 Diagnostics, LLC
Department
Type
DUNS #
142406110
City
New Haven
State
CT
Country
United States
Zip Code
06530