EGFR Peptides as Vaccines in Anti-Tumor Immunity

描述（由申请人提供）：我们I期研究的重点是开发一种新的基于肽的疫苗接种策略，旨在克服对表皮生长因子受体（EGFR）肿瘤抗原的免疫耐受。EGFR表达与肿瘤发展的严重程度之间的直接相关性使这种表面蛋白成为治疗的重要靶点。事实上，EGFR在大多数实体肿瘤中都是过表达的，包括结肠癌、乳腺癌、头颈癌、非小细胞肺癌、膀胱癌、胶质瘤、肾癌、肾癌和卵巢癌。EGFR是erbB家族的一种170 kda的跨膜糖蛋白。与该家族中的其他蛋白（如Her-2）类似，EGFR由细胞外受体结构域、跨膜区域和具有酪氨酸激酶功能的细胞内结构域组成。现有的EGFR特异性疗法是酪氨酸激酶信号功能的抑制剂和针对EGFR蛋白的单克隆抗体，Erbitux和Panitumumab。抗体治疗已被观察到与传统化疗有协同作用。这些昂贵的治疗方法被持续地给予患者，直到观察到肿瘤无反应。

DESCRIPTION (provided by applicant): 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.