Optimizing T cell Immunity to Cancer Vaccines

优化 T 细胞对癌症疫苗的免疫

• 批准号: 7111001
• 负责人: MIGUEL-ANGEL PERALES
• 金额: $ 13.47万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7111001
• 关键词: CD28 molecule; CD4 molecule; DNA; T lymphocyte; active immunization; cellular immunity; cytokine; cytotoxic T lymphocyte; differentiation antigens; disease /disorder model; gene expression; human genetic material tag; immune tolerance /unresponsiveness; immunologic memory; immunomodulators; laboratory mouse; melanoma; neoplasm /cancer immunology; neoplasm /cancer vaccine; postdoctoral investigator; technology /technique development; tumor antigens; vector vaccine

DESCRIPTION (provided by applicant): This proposal describes a four-year training program for the development of an academic career in Laboratory Medicine. The principal investigator has completed fellowship training in Medical Oncology at Memorial Sloan-Kettering Cancer Center and will now expand upon his scientific skills through a unique integration of interdepartmental resources. Alan Houghton will mentor the principal investigator's scientific development. Dr. Houghton is Chairman of the Immunology Program and Chief of the Clinical Immunology Service at MSKCC, and an authority on tumor immunology. To enhance the training, the program will enlist the expertise of Dr. Eric Pamer, Chief of the Infectious Disease Service at MSKCC, and a recognized expert on the use of mouse models for the study of T cell responses to pathogens. In addition, an advisory committee of highly regarded medical scientists will provide scientific and career advice. Research will focus on the generation of T cell memory responses to melanoma differentiation antigens in a mouse pre-clinical model. The specific aims include: (1) Characterizing the generation of CD8+ T cells against melanoma differentiation antigens by xenogeneic DNA immunization; (2) Investigating mechanisms necessary for the maintenance of CD8+ T cells specific for differentiation antigens, including the role of antigen expression, CD4 help and immune tolerance; and (3) Developing strategies to induce memory T cells against tumor antigens, including the co-delivery of cytokine genes acting as molecular adjuvants, and examining the effects of CTLA-4 blockade and regulatory T cells. These studies are directly relevant to a class of common antigens expressed by many if not most human cancers and hopefully will lead to improved strategies for immunization against these antigens in humans with cancer. The Department of Medicine at Memorial Sloan-Kettering Cancer Center provides an ideal setting for training physician scientists by incorporating expertise from diverse resources into customized programs. This environment maximizes the potential for the principal investigator to establish a successful independent research program.

描述（由申请人提供）：该提案描述了一个为期四年的检验医学学术职业发展培训计划。 首席研究员已在纪念斯隆-凯特琳癌症中心完成了肿瘤内科进修培训，现在将通过独特的跨部门资源整合来扩展他的科学技能。 艾伦·霍顿将指导首席研究员的科学发展。 Houghton 博士是 MSKCC 免疫学项目主席兼临床免疫学服务主管，也是肿瘤免疫学领域的权威。 为了加强培训，该项目将聘请 MSKCC 传染病服务部主任 Eric Pamer 博士的专业知识，他是使用小鼠模型研究 T 细胞对病原体反应的公认专家。 此外，由备受尊敬的医学科学家组成的咨询委员会将提供科学和职业建议。 研究重点是在小鼠临床前模型中产生针对黑色素瘤分化抗原的 T 细胞记忆反应。 具体目标包括：（1）通过异种DNA免疫表征针对黑色素瘤分化抗原的CD8+T细胞的产生； (2) 研究维持对分化抗原具有特异性的CD8+ T细胞所必需的机制，包括抗原表达、CD4帮助和免疫耐受的作用； (3) 制定诱导记忆 T 细胞对抗肿瘤抗原的策略，包括共同递送作为分子佐剂的细胞因子基因，并检查 CTLA-4 阻断和调节性 T 细胞的作用。 这些研究与许多（如果不是大多数）人类癌症表达的一类常见抗原直接相关，并有望改进癌症患者针对这些抗原的免疫策略。 纪念斯隆-凯特琳癌症中心的医学系通过将不同资源的专业知识融入定制项目，为培训医师科学家提供了理想的环境。 这种环境最大限度地发挥了首席研究员建立成功的独立研究计划的潜力。