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）：所提出的研究旨在通过使用异丙基修饰的肽来破坏对乳腺癌细胞上的“自身”肿瘤抗原的免疫耐受来开发新的肿瘤免疫疗法。大多数肿瘤抗原被表征为正常的、非突变的自身肽，将自身免疫的概念与肿瘤免疫的发展联系起来。以往的研究表明，异种肽抗原疫苗可以克服免疫耐受。我们假设，异丙基修饰的肽可以激活肿瘤反应性免疫应答，导致肿瘤减少或消除。这一假设得到了我们使用小鼠自身免疫模型的初步研究的支持。用异丙基修饰的肽免疫产生细胞毒性（杀伤）T细胞和对“自身抗原”的体液免疫应答。“拟议的研究将把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HER-2/neu“自身”肿瘤抗原中选定表位的异丙基修饰肽免疫neu转基因小鼠。然后，我们将在这种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isoapartyl修饰的肽疫苗，该疫苗将克服乳腺癌患者的免疫耐受，并将先前存在的对HER-2/neu的免疫力提高到治疗水平。