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EGFR Peptides as Vaccines in Anti-Tumor Immunity

EGFR 肽作为抗肿瘤免疫疫苗

基本信息

批准号：
7330500
负责人：
Mark J Mamula
金额：
$ 27.77万
依托单位：
L2 DIAGNOSTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7330500
关键词：
Adjuvant Animals Antibodies Antibody Formation Antibody Therapy Applications Grants Autoantigens B-Lymphocytes Binding CD8-Positive T-Lymphocytes Canada Cell Adhesion Cell Extracts Cell Proliferation Clinical Trials Colon Carcinoma Condition Data Development Diagnostic Economics Epidermal Growth Factor Receptor Erbitux Family Flow Cytometry Future Glioma Glycoproteins Government Growth Guanosine Monophosphate Head and Neck Cancer Healthcare Industry Human Immune Immune Tolerance Immune response Immunization Immunoblotting Immunologics In Vitro Lung Lung Neoplasms Malignant neoplasm of kidney Malignant neoplasm of ovary Mediating Medical Surveillance Membrane Proteins Monoclonal Antibodies Monoclonal Antibody Therapy Mus Non-Small-Cell Lung Carcinoma Patients Peptide Vaccines Peptides Phase Phase I Clinical Trials Phase II Clinical Trials Property Protein Binding Protein Overexpression Protein Tyrosine Kinase Proteins Renal carcinoma Reporting Research Severities Signal Transduction Solid Neoplasm T memory cell T-Lymphocyte Therapeutic Therapeutic Monoclonal Antibodies Tissues Transmembrane Domain Tumor Antigens Tumor Immunity Tyrosine Kinase Inhibitor United Kingdom Vaccination Vaccines Work aluminum sulfate base bladder Carcinoma cancer therapy cell growth chemotherapy clinical efficacy cost cost effective design extracellular human disease in vivo malignant breast neoplasm mouse model neoplastic cell novel novel strategies panitumumab peptide based vaccine polyclonal antibody prevent receptor receptor expression response success theories tumor tumor growth vaccination strategy

项目摘要

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.

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表达与肿瘤发展严重程度之间的直接相关性使这种表面蛋白成为重要的治疗靶点。事实上，EGFR在大多数实体瘤中过表达，包括结肠癌、乳腺癌、头颈癌、非小细胞肺癌、膀胱癌、神经胶质瘤、肾癌、肾癌和卵巢癌。EGFR是erbB家族的170-kDa跨膜糖蛋白。类似于该家族中的其他蛋白质，例如Her-2，EGFR由细胞外受体结构域、跨膜区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传导功能的抑制剂和针对EGFR蛋白的单克隆抗体爱必妥和帕尼单抗。已观察到抗体疗法与传统化疗具有协同作用。这些昂贵的治疗持续给予患者，直到观察到肿瘤无反应。我们的建议将检查EGFR蛋白的选定肽打破免疫耐受和抑制EGFR肿瘤细胞生长的能力。我们使用EGFR和Her-2肽的初步数据支持这种方法的有效性。I期研究： 1.我们将利用隐蔽的和修饰的EGFR肽进行免疫，并检查抗肿瘤B和T细胞免疫应答的发展。 2.我们将评估抗肿瘤免疫在体外和体内阻止人和鼠携带EGFR的肿瘤细胞生长的能力。我们的工作将利用小鼠模型来比较爱必妥抗体治疗与爱必妥的抗肿瘤反应与EGFR肽疫苗接种引起的多克隆抗体反应。这些研究将潜在地提供单独使用或与传统化疗组合使用的新颖且易于应用的治疗策略，其可以以有效且具有成本效益的方式引发长期抗肿瘤免疫。