Nanomedicine development center for mechanobiology

B。抽象和具体目标 我们中心的目标是：1）阐明T细胞的机械生物学; 2）利用对T细胞的理解， 机械生物学，开发新的T细胞培养系统和工程化T细胞，以改善治疗。 免疫疗法克服了许多限制疫苗策略的障碍，通过过继性转移T细胞， 具有受控抗原特异性的细胞。此外，T细胞的离体培养允许产生大的T细胞。 T细胞的数量，这在面对癌症中的T细胞缺陷时至关重要。一股主要的潮流 过继性免疫治疗的挑战是控制T细胞的自我更新潜力，这通常在 免疫学称为“记忆”，因为它允许免疫系统维持更高频率的特异性T细胞， 病原体的早期发现另一个问题是效应群体如Th 17的自我更新能力 在过继免疫治疗模型中高效的CD 4细胞。因此，通过将该属性设计为 在过继免疫治疗中使用T细胞，治疗的即时和长期效果都可能是 提高我们的NDC假设IS整合了化学和机械信号，以确定 T细胞分化的过程。因此，我们中心的一个主要目标是通过控制免疫系统来改善免疫治疗。 表型和功能的体外扩增的T细胞和可扩展的数量。我们将专注于免疫治疗 包括白血病和实体瘤在内的癌症。除了使用过继免疫疗法选择性地 并直接攻击肿瘤或肿瘤间质，免疫疗法可用于保护患者免受 免疫病理学是由治疗努力引起的。在造血细胞治疗白血病的过程中 造血干细胞移植（HCT），其目的是用造血和免疫细胞重建接受者， 化疗后，供体T细胞可引起移植物抗宿主病（GVHD）-一种重要的发病来源 和HCT后的死亡率。目前预防GVHD的方法依赖于使用常规药物， 并经常导致免疫缺陷，是不令人满意的，新的GVHD预防方法显然是可行的。 needed.因此，在提高患者生存率和生活质量的目标下，我们还计划利用 调节性T细胞（TcR）通过调节Treg功能保护患者免受GVHD毒性作用， 力量

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.