Modified HER-2 Tumor Antigens for Vaccination in Cancer

用于癌症疫苗接种的修饰 HER-2 肿瘤抗原

• 批准号: 6742316
• 负责人: Mark J Mamula
• 金额: $ 9.99万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6742316
• 关键词: biotechnology; breast neoplasms; cell line; enzyme linked immunosorbent assay; genetically modified animals; histology; immune response; immunocytochemistry; laboratory mouse; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; neoplastic process; peptides; protooncogene; tumor antigens; vaccine development

DESCRIPTION (provided by applicant): The proposed studies are aimed at developing a new tumor immunotherapy by using isoaspartyl-modified peptides to break immune tolerance to "self" tumor antigens on breast cancer cells. 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 demonstrated that vaccination with xenogenic peptide antigens could overcome immune tolerance. We hypothesize that isoaspartyl-modified peptides can activate tumor reactive immune responses that lead to tumor reduction or elimination. This hypothesis is supported by our preliminary studies using a murine model of autoimmunity. Immunization with isoaspartyl-modified peptides generated cytotoxic (killer) T cells and humoral immune responses to "self antigens." The proposed studies will extend these observations to a transgenic mouse model of mammary tumors. We will immunize neu transgenic mice with isoaspartyl-modified peptides representing selected epitopes in the oncogenic HER-2/neu "self" tumor antigen. We will then examine tumor-specific immune responses, tumor regression, and histology in this genetic mouse mammary tumor model that resembles human breast cancer. Our long-term goal is to develop an isoapartyl-modified peptide vaccine that will overcome immune tolerance in breast cancer patients, and enhance pre-existing immunity to HER-2/neu to therapeutic levels.

描述（由申请人提供）：拟议的研究旨在通过使用异肥大剂改性肽来开发新的肿瘤免疫疗法，以破坏乳腺癌细胞上“自我”肿瘤抗原的免疫耐受性。大多数肿瘤抗原的表征是正常的，非突变的自肽，将自身免疫性的概念与肿瘤免疫的发展联系起来。先前的研究表明，用异种肽抗原疫苗接种可以克服免疫耐受性。我们假设异源天载体修饰的肽可以激活肿瘤反应性免疫反应，从而导致肿瘤减少或消除。我们使用自身免疫模型的初步研究支持了这一假设。用异冬氨酰改性肽免疫产生的细胞毒性（杀伤）T细胞和对“自抗原”的体液免疫反应。拟议的研究将将这些观察结果扩展到乳腺肿瘤的转基因小鼠模型。我们将用代表致癌性HER-2/NEU“自我”肿瘤抗原中选定的表位的等载体修饰的肽对NEU转基因小鼠进行免疫。然后，我们将在类似于人类乳腺癌的遗传小鼠乳腺肿瘤模型中检查肿瘤特异性免疫反应，肿瘤消退和组织学。我们的长期目标是开发一种异甲酰胺反应的肽疫苗，该疫苗将克服乳腺癌患者的免疫耐受性，并增强对HER-2/NEU对治疗水平的免疫力。