Nanomedicine development center for mechanobiology

机械生物学纳米医学发展中心

• 批准号: 8791721
• 负责人: Michael Loran Dustin
• 金额: $ 17.42万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8791721
• 关键词: Address; Adoptive Immunotherapy; Antigenic Specificity; Behavior Control; Biology; CD34 gene; CD4 Positive T Lymphocytes; Cell Culture System; Cell Differentiation process; Cell Transplants; Cells; Chemicals; Clinic; Clinical; Computational Biology; Cytoprotection; Dendritic Cells; Development; Diffusion; Engineering; Frequencies; Gene Expression; Generations; Goals; Hematopoietic; Human; Immune; Immune system; Immunologic Deficiency Syndromes; Immunology; Immunotherapy; Lead; Life; Long-Term Effects; Malignant Neoplasms; Mechanics; Memory; Modeling; Morbidity - disease rate; Mus; Nature; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Physics; Population; Positioning Attribute; Pre-Clinical Model; Preventive; Property; Quality of life; Regulatory T-Lymphocyte; Signal Transduction; Small Interfering RNA; Solid Neoplasm; Source; Surface; T cell differentiation; T memory cell; T-Lymphocyte; Testing; Therapeutic; Toxic effect; Vaccines; abstracting; base; cancer immunotherapy; cell type; chemotherapy; graft vs host disease; immunopathology; improved; in vivo; inhibitor/antagonist; leukemia; lymph nodes; mortality; mouse model; multidisciplinary; nano; nanomedicine; nanoparticle; novel; pathogen; pre-clinical; prevent; reconstitution; research clinical testing; scale up; self-renewal; small molecule; tumor; Address; Adoptive Immunotherapy; Antigenic Specificity; Behavior Control; Biology; CD34 gene; CD4 Positive T Lymphocytes; Cell Culture System; Cell Differentiation process; Cell Transplants; Cells; Chemicals; Clinic; Clinical; Computational Biology; Cytoprotection; Dendritic Cells; Development; Diffusion; Engineering; Frequencies; Gene Expression; Generations; Goals; Hematopoietic; Human; Immune; Immune system; Immunologic Deficiency Syndromes; Immunology; Immunotherapy; Lead; Life; Long-Term Effects; Malignant Neoplasms; Mechanics; Memory; Modeling; Morbidity - disease rate; Mus; Nature; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Physics; Population; Positioning Attribute; Pre-Clinical Model; Preventive; Property; Quality of life; Regulatory T-Lymphocyte; Signal Transduction; Small Interfering RNA; Solid Neoplasm; Source; Surface; T cell differentiation; T memory cell; T-Lymphocyte; Testing; Therapeutic; Toxic effect; Vaccines; abstracting; base; cancer immunotherapy; cell type; chemotherapy; graft vs host disease; immunopathology; improved; in vivo; inhibitor/antagonist; leukemia; lymph nodes; mortality; mouse model; multidisciplinary; nano; nanomedicine; nanoparticle; novel; pathogen; pre-clinical; prevent; reconstitution; research clinical testing; scale up; self-renewal; small molecule; tumor

B. Abstract and Specific Aims The goals of our center are to 1) elucidate the mechanical biology of T cells 2) use this understanding of T cell mechanical biology to develop novel T cell culture systems and engineered T cells for improved therapeutics. Adoptive immunotherapy overcomes many obstacles that limit vaccine strategies, by adoptively transferring T cells with controlled antigenic specificity. In addition, ex vivo culture of T cells allows for the generation of large numbers of T cells, which is of utmost importance in the face of T cell deficiencies in cancer. A major current challenge in adoptive immunotherapy is to control self-renewal potential of T cell, often referred to in immunology as "memory", as it allows the immune system to maintain a higher frequency of T cells specific for pathogens encountered earlier. Another issue is self-renewal capacity in effector populations such as Th17 CD4 cells that are high effective in adoptive immunotherapy models. Hence, by engineering this property into T cells used in adoptive immunotherapy, both the immediate and long-term effects of therapy could be improved. Our NDC hypothesized that the IS integrates chemical and mechanical signals to determine the course of T cell differentiation. A major goal of our center is thus to improve immunotherapy by controlling the phenotype and function of ex vivo expanded T cells and in scalable numbers. We will focus on immunotherapy of cancers including both leukemias and solid tumors. Besides using adoptive immunotherapy to selectively and directly attack the tumor or tumor stroma, immunotherapy can be used to protect the patient from immunopathology resulting from treatment efforts. During treatment of leukemia by hematopoietic cell transplant (HCT), which aims at reconstituting the recipient with hematopoietic and immune cells post chemotherapy, donor T cells can cause graft-versus-host-disease (GVHD) - a significant source of morbidity and mortality post-HCT. Current approaches to prevent GVHD, which rely on the use of conventional drugs, and often lead to immunodeficiency, are not satisfactory and new GVHD preventive approaches are clearly needed. Therefore, within our goal of improving patient survival and quality of life, we also plan to make use of regulatory T cells (Tregs) to protect patients from the GVHD toxic effect by modulating Treg function and potency.

B.摘要和具体目的 我们中心的目标是1）阐明T细胞的机械生物学2）使用T细胞的理解 机械生物学开发新型T细胞培养系统和设计的T细胞，以改善治疗疗法。 收养免疫疗法克服了许多限制疫苗策略的障碍 具有受控抗原特异性的细胞。另外，T细胞的离体培养可以产生大型 T细胞的数量，这对于面对癌症的T细胞缺乏至关重要。主要电流 收养免疫疗法的挑战是控制T细胞的自我更新潜力，通常提到 免疫学为“记忆”，因为它允许免疫系统维持更高的T细胞频率 病原体早些时候遇到。另一个问题是效应人群（例如TH17）的自我更新能力 在收养免疫疗法模型中高效的CD4细胞。因此，通过将此属性工程 T细胞用于收养免疫疗法，治疗的直接和长期影响都可以 改进。我们的NDC假设IS是整合化学和机械信号，以确定 T细胞分化的过程。因此，我们中心的主要目标是通过控制 Ex Vivo的表型和功能扩展了T细胞和可扩展的数字。我们将专注于免疫疗法 包括白血病和实体瘤在内的癌症。除了使用收养免疫疗法选择性 直接攻击肿瘤或肿瘤基质，可以使用免疫疗法来保护患者免受 治疗工作引起的免疫病理学。在造血细胞治疗白血病期间 移植（HCT），旨在用造血和免疫细胞重建受体 化学疗法，供体T细胞会引起移植物抗宿主 - 疾病（GVHD） - 发病率的重要来源 和HCT死亡率。当前预防依赖常规药物的GVHD的方法， 而且通常会导致免疫缺陷，并不令人满意，而新的GVHD预防方法显然是 需要。因此，在我们改善患者生存和生活质量的目标中，我们还计划利用 调节性T细胞（Tregs）通过调节Treg功能和 效力。