CD8 + CD75s + regulatory T cells in anti-tumor immunity

CD8 CD75s 调节性 T 细胞在抗肿瘤免疫中的作用

• 批准号: 7120525
• 负责人: JAMES C. ZIMRING
• 金额: $ 12.8万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120525
• 关键词: active immunization; antitumor antibody; autoantigens; autoimmunity; cell population study; cell transplantation; cellular immunity; disease /disorder model; flow cytometry; genetically modified animals; immune tolerance /unresponsiveness; immunomodulators; laboratory mouse; monoclonal antibody; neoplasm /cancer immunology; neoplasm /cancer vaccine; nonhuman therapy evaluation; sialyltransferases; spleen transplantation; suppressor T lymphocyte; surface antigens; vaccine evaluation

DESCRIPTION (provided by applicant): The main long-term objective of this Mentored Clinical Scientist Development Award is to provide the candidate with the guidance and training necessary to successfully make the transition to an investigator with an independent research program. This goal will be accomplished primarily through mentored bench work with a focus on broadening the knowledge and technical expertise of the applicant in the areas of cellular and molecular tumor immunology. Instruction in proper scientific method and procedure including reporting of data through publication will be provided. The applicant will also be provided the opportunity to become an interactive member of the broader scientific community through presentation of data at scientific meetings and participation in seminars and journal clubs. The research proposal is focused on an investigation of the role of negative regulatory T cells in a mouse tumor model. These studies are based upon the observation that transient elimination of negative regulatory T cells, using an antibody specific for CD75s, results in spontaneous tumor regression and lasting anti-tumor immunity. The proposed studies are designed to elucidate the mechanism by which model tumors evade immune destruction and the role that negative regulatory T cells play in this process. Since immunological tolerance to tumor antigens represents a major hurdle in the development of efficacious tumor vaccines, a thorough understanding of this system may contribute to both our basic understanding of tumor immunology and the successful implementation of tumor immunotherapy. Three hypothesis based specific aims are presented including experimental design, predicted outcomes, and potential problems. These aims propose to investigate the role that negative regulatory T cells play in the establishment of immunological tolerance to tumor antigens and the fashion in which their elimination can result in tumor rejection.

描述（由申请人提供）：这一指导的临床科学家发展奖的主要长期目标是为候选人提供成功通过独立研究计划过渡到调查员所必需的指导和培训。该目标将主要通过有指导的基准工作来实现，重点是扩大细胞和分子肿瘤免疫学领域的申请人的知识和技术专长。将提供适当的科学方法和程序的指导，包括通过出版的数据报告。还将为申请人提供机会，通过在科学会议上介绍数据并参加研讨会和期刊俱乐部，成为更广泛的科学界的互动成员。 研究建议的重点是研究负调控T细胞在小鼠肿瘤模型中的作用。这些研究基于以下观察结果：使用CD75S的抗体瞬时消除阴性T细胞会导致自发性肿瘤消退和持久的抗肿瘤免疫力。拟议的研究旨在阐明模型肿瘤逃避免疫破坏的机制以及阴性调节性T细胞在此过程中的作用。由于对肿瘤抗原的免疫耐受性代表了有效肿瘤疫苗发展的主要障碍，因此对该系统的透彻理解可能有助于我们对肿瘤免疫学的基本理解和成功实施肿瘤免疫疗法。提出了三个基于假设的特定目标，包括实验设计，预测的结果和潜在问题。这些目的建议调查负调控T细胞在建立对肿瘤抗原的免疫耐受性以及消除可能导致肿瘤排斥的方式的作用。