DENDRITIC CELL IMMUNIZATION OF PRETERM NEONATES

描述：(申请人提供) 背景：树突状细胞是一种抗原提呈细胞，在 在适应性免疫调节中的作用。最近，方法已经变成了 可用于从各种来源分离这些细胞，包括CORD 血液、外周血和骨髓。这引发了人们对 这些细胞的潜在治疗用途。 目标：本提案的主要目标是确定 脐带血来源的树突状细胞作为治疗药物的可行性 早产儿传染病的防治。特定的 目的是1)鉴定新鲜分离的和培养的树突状细胞 脐带血和成人外周血产生的细胞，2)到 新生儿树突状细胞作为抗原的功能评价 提出细胞，以及3)开发实用的自体DC方法 分离、储存和抗原装载。方法：将树突状细胞 用免疫磁性分离法从脐带血和成人血中提取 技巧。新鲜分离培养的脐带和成人树突状细胞 将比较细胞表面谱系标记的表达，主要是 组织相容性分子、黏附分子、共刺激分子和 细胞因子受体。此外，还将评估脐带和成体树突状细胞 它们的功能包括诱导幼稚T细胞的能力 激活和增殖并刺激B细胞成熟为抗体 产生浆细胞。 与健康相关：传染病是一个重大问题 极低出生体重(VLBW)新生儿在重症监护病房住院 单位(NICU)。约25%的极低出生体重新生儿(出生体重在 500克和1500克)在NICU经历中至少有一次记录在案 在他们住院期间的脓毒症。因暴露延长住院时间 对于耐药生物和多重侵入性程序，在存在 免疫不成熟使这些婴儿容易感染医院获得性疾病 感染。树突状细胞可能是理想的免疫载体 感染剂。树突状细胞已被证明呈现细菌和 病毒抗原在体外对T细胞的作用。动物研究作为抗原是令人鼓舞的 脉冲树突状细胞在提供保护性免疫方面有效。 水平等于或大于常规佐剂所建立的水平 疫苗。到目前为止，对人类的研究一直局限于I/II阶段到 成人志愿者和晚期恶性肿瘤患者的调查 疾病。

DESCRIPTION: (Provided by Applicant) Background: Dendritic cells are antigen presenting cells that play a critical role in regulation of adaptive immunity. Recently, methods have become available to isolate these cells from a variety of sources including cord blood, peripheral blood, and bone marrow. This has sparked interest in potential therapeutic use of these cells. Objectives: The primary objective of this proposal is to determine the feasibility of using cord blood derived dendritic cells as agents for prevention and treatment of infectious diseases in preterm infants. Specific aims are 1) to characterize freshly isolated and culture-derived dendritic cells generated from umbilical cord blood and adult peripheral blood, 2) to evaluate the functional capabilities of neonatal dendritic cell as antigen presenting cells, and 3) to develop practical methods for autologous DC isolation, storage, and antigen loading. Methods: Dendritic cells will be obtained from cord blood and adult blood using immunomagnetic separation techniques. Freshly isolated and culture-derived cord and adult dendritic cells will be compared for surface expression of lineage markers, major histocompatibility molecules, adhesion molecules, co-stimulatory molecules and cytokine receptors. Also, cord and adult dendritic cells will be evaluated for their functional capabilities including their ability to induce naive T cell activation and proliferation and to stimulate B cell maturation into antibody producing plasma cells. Health Relatedness: Infectious diseases represent a significant problem for very low birth weight (VLBW) infants hospitalized in Newborn Intensive Care Units (NICU). Approximately 25 percent of VLBW neonates (birth weight between 500 and 1500 grams) in the NICU experience at least one documented episode of sepsis during their hospital course. Prolonged hospitalization with exposure to resistant organisms and multiple invasive procedures, in the presence of immunologic immaturity renders these infants vulnerable to hospital-acquired infections. Dendritic cells may be ideal vehicles for immunization against infectious agents. Dendritic cells have been shown to present bacterial and viral antigens to T cells in vitro. Animal studies are encouraging as antigen pulsed dendritic cells are efficacious in providing protective immunity at a level equal to or greater than that established by conventional adjuvant vaccines. To date, studies in humans have been limited phase I/II to investigations in adult volunteers and in patients with advanced malignant diseases.