Nanostructures For Engineering Immune Responses of Dendritic Cells

用于工程树突状细胞免疫反应的纳米结构

基本信息

批准号：
8517374
负责人：
GANG-YU LIU
金额：
$ 17.57万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8517374
关键词：
Antigen Presentation Antigens Appearance Atomic Force Microscopy Basic Science Binding Biological Assay CD4 Positive T Lymphocytes CD8B1 gene Cell Therapy Cell membrane Cells Chickens Coculture Techniques Complex Culture Media Cytolysis Data Dendritic Cell Vaccine Dendritic Cells Engineering Enzyme-Linked Immunosorbent Assay Exhibits Exposure to Filopodia Fluorescence Future Harvest Image Immune Immune response Immune system Immunity Immunology Immunotherapy In Situ In Vitro Inflammatory Response Investigation Isotopes Knowledge Label Laboratories Ligands Lipopolysaccharides Measures Membrane Methods Modeling Molecular Morphology Nanoarray Analytical Device Nanostructures Nanotechnology Outcome Ovalbumin Phenotype Physiologic pulse Play Positioning Attribute Proliferating Protocols documentation Regulation Research Role Series Signal Transduction Solid Spatial Design Stem cells Surface T cell response T-Cell Proliferation T-Lymphocyte Tissue Engineering Toll-like receptors Training Translational Research adaptive immunity base cancer therapy cytokine cytotoxic cytotoxicity improved in vivo killings melanoma nanofabrication nanoscale neoplastic cell programs public health relevance toll-like receptor 4 tumor vaccine development

项目摘要

DESCRIPTION (provided by applicant): The objective of this R21 proposal is to demonstrate the concept that engineered nanostructures of ligands provide a highly effective platform for the investigation and programming of the immune response of dendritic cells (DCs). Taking advantage of exquisite spatial precision, enabled by a nanofabrication method known as atomic force microscopy (AFM)-based nanografting which was invented in the PI's laboratory, chosen ligands such as lipopolysaccharide(LPS) molecules, are accurately positioned on supports with designed spatial arrangement and numbers for recognition by toll-like receptors (TLRs) such as TLR-4 on DCs' membrane surface. By varying the number and spatial arrangement of ligands in the nanostructures, in conjunction with antigen pulsing, desired immune responses could be attained and harnessed for anti-tumor therapy. This approach is based upon the hypothesis - validated by our preliminary studies and current knowledge of DC immunology - that clustering of ligand-TLR complexes dictates subsequent immune signaling cascades, such as maturation and antigen presentation. The concept differs intrinsically from currently in vitro approaches due to its molecular level control of the number and the distributions of ligand-TLR complexes. As such, DCs with desired immune profiles could be engineered and generated for subsequent translational research and in vivo applications including tissue engineering, and DC vaccine development for anti-cancer therapy, and T-cell anti-tumor therapy.

描述（由申请人提供）：该R21提案的目的是证明配体的工程纳米结构为树突状细胞（DCS）免疫反应的研究和编程提供了一个高效的平台。利用精美的空间精度，通过在PI的实验室中发明的纳米化方法（称为原子力显微镜（AFM）的基于原子力显微镜（AFM）的纳米级，选择的配体（例如脂多糖（LPS）分子）在设计中被精确定位（诸如Spatial和数字），以确定脂多糖（LPS）分子的含量（LPS）分子，并将其定位为TOLLICE（TOLLS）。 DCS的膜表面上的TLR-4。通过改变配体在纳米结构中的数量和空间排列，结合抗原脉冲，可以获得所需的免疫反应，并利用用于抗肿瘤疗法。这种方法是基于我们的初步研究和当前对DC免疫学的知识来验证的假设，即配体-TLR复合物的聚类决定了随后的免疫信号级联反应，例如成熟和抗原呈递。由于其分子水平控制配体-TLR复合物的分子水平和分布，该概念与当前在体外方法的本质不同。因此，具有所需免疫特征的DC可以进行设计和生成，用于随后的翻译研究和体内应用，包括组织工程以及用于抗癌治疗的DC疫苗开发以及T细胞抗肿瘤疗法。