The focus of our in Phase I studies is the development of a novel peptide-based vaccination strategy designed to overcome immune tolerance to Epidermal Growth Factor Receptor (EGFR) tumor antigen. The direct correlation between EGFR expression and the severity of tumor development makes this surface protein an important target of therapy. Indeed, EGFR is overexpressed in a majority of solid tumors including colon cancer, breast cancer, head-and-neck cancer, non-small-cell lung cancer, bladder carcinomas, gliomas, kidney cancer, renal cancer, and ovarian cancer. EGFR is a 170-kDa transmembrane glycoprotein of the erbB family. Similar to other proteins in this family, such as Her-2, EGFR consists of an extracellular receptor domain, a transmembrane region, and an intracellular domain with tyrosine kinase function. The existing EGFR-specific therapies are inhibitors of the tyrosine kinase signaling functions and the monoclonal antibodies, Erbitux and Panitumumab, directed at the EGFR protein. Antibody therapy has been observed to be synergistic with traditional chemotherapy. These expensive therapies are administered to patients on a continuing basis until unresponsiveness of the tumor is observed. ? Our proposal will examine the ability of selected peptides of the EGFR protein to break immune tolerance and inhibit EGFR-tumor cell growth. Our preliminary data from the use of both EGFR and Her-2 peptides support the efficacy of this approach. In phase I studies: ? 1. We will utilize cryptic and modified EGFR peptides for immunization and examine the development of both anti-tumor B and T cell immune responses. ? 2. We will assess the ability of anti-tumor immunity to prevent growth of human and murine EGFR-bearing tumor cells in vitro and in vivo. ? Our work will utilize a mouse model to compare the anti-tumor responses of Erbitux antibody therapy with Erbitux to the polyclonal antibody responses elicited by EGFR peptide vaccination. The studies will potentially provide a novel and easily applied therapeutic strategy to be used alone or in combination with traditional chemotherapies that can elicit long term anti-tumor immunity in an efficient and cost effective manner. ? ?
| Doyle, Hester A; Koski, Raymond A; Bonafé, Nathalie et al. (2018) Epidermal growth factor receptor peptide vaccination induces cross-reactive immunity to human EGFR, HER2, and HER3. Cancer Immunol Immunother 67:1559-1569 |
