Nanomedicine development center for mechanobiology

B.抽象目标和具体目标 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细胞的这种理解 机械生物学，开发新的T细胞培养系统和工程T细胞，以改进治疗。 过继免疫疗法克服了限制疫苗策略的许多障碍，通过过继转移T细胞 具有受控抗原特异性的细胞。此外，T细胞的体外培养允许产生大的 T细胞的数量，这在面对癌症中T细胞缺陷的情况下是至关重要的。一股主要水流 过继免疫治疗的挑战是控制T细胞的自我更新潜力，这通常被称为 免疫学被称为“记忆”，因为它允许免疫系统保持更高频率的T细胞特异性 之前遇到的病原体。另一个问题是Th17等效应器种群的自我更新能力 在过继免疫治疗模型中高效的CD4细胞。因此，通过将该属性设计为 T细胞在过继免疫治疗中的应用，治疗的即时和长期效果都可能是 改进了。我们的NDC假设IS综合了化学和机械信号来确定 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 体外扩增的T细胞的表型和功能以及可伸缩的数量。我们将专注于免疫疗法 包括白血病和实体瘤在内的癌症。除了使用过继免疫疗法选择性地 并直接攻击肿瘤或肿瘤间质，可用免疫疗法保护患者免受 由于治疗努力而导致的免疫病理学。造血细胞在白血病治疗中的应用 移植(HCT)，其目的是在移植后重建受者的造血和免疫细胞 化疗，供者T细胞可导致移植物抗宿主病(GVHD)--发病率的一个重要来源 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，都不令人满意，新的GVHD预防方法显然是 需要的。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Tregs来保护患者免受GVHD毒性效应 威力。

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.