Tunable DNA-nanostructure to induce NK-mediated killing of tumor cells

可调节 DNA 纳米结构诱导 NK 介导的肿瘤细胞杀伤

• 批准号: 7990183
• 负责人: YUNG CHANG
• 金额: $ 19.34万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990183
• 关键词: Activated Natural Killer Cell; Antibodies; Aptamer Technology; B-Cell Lymphomas; Binding; Cell Line; Cells; Complex; DNA; Disease; Effector Cell; Engineering; Figs - dietary; Goals; Human; Immune; Immune response; Immunity; Interleukin-2; Libraries; Ligands; Link; Magic; Malignant - descriptor; Mediating; Modeling; Molecular; Nanostructures; Natural Immunity; Natural Killer Cells; Nature; Nucleic Acids; Positioning Attribute; Process; Signal Pathway; T-Lymphocyte; Therapeutic; aptamer; base; cancer cell; cancer diagnosis; cancer therapy; crosslink; cytokine; cytotoxicity; design; immune activation; killings; microbial; nanoscale; neoplastic cell; novel; pathogen; programs; public health relevance; response; scaffold; tumor

DESCRIPTION (provided by applicant): Tunable DNA-nanostructure to induce NK-mediated killing of tumor cells Summary Antibodies are important recognition molecules that have been widely used in cancer diagnosis and cancer therapy. Aptamers, which are nucleic acid-based recognition molecules, have also been exploited for biomedical applications, partly attributed to their robust nature in synthesis and selection for specific binding activity, similar to antibodies. We propose to develop multivalent aptamers linked onto tunable DNA-nanostructure that bind specifically to both the effector cell and tumor cells, thus are able to engage their interactions, which will trigger the activation of immune effector cells to facilitate destruction of tumor cells. We will focus on constructing multi-valent and multi-specific aptamers linked on DNA-nanoscaffolds to direct natural killer (NK) cells to attack tumor cells. This will be achieved by combining rational design of programmable DNA-nanoscaffolds with systemic selection of aptamer libraries. In addition, the scalable feature of the DNA-nanostructure platform makes it possible to incorporate additional immune modulating ligands to coordinate and synergize various lines of host immunity against cancer cells, including both humoral and cellular immune responses. Thus, these aptamer DNA-nanostructures can potentially function as "magic bullets" for cancer therapy, as well as therapeutics for other diseases. PUBLIC HEALTH RELEVANCE: We propose to develop a novel tumor-killing DNA-nanostructure, in which multimeric cell- recognition aptamers will be assembled onto tunable and programmable DNA-nanoscaffolds to engage immune cells to attack tumor cells.

描述（由申请人提供）：诱导NK介导的肿瘤细胞杀伤的可调DNA纳米结构概述抗体是重要的识别分子，已广泛用于癌症诊断和癌症治疗。适体是基于核酸的识别分子，也已被开发用于生物医学应用，部分归因于其在合成和选择特异性结合活性方面的稳健性质，类似于抗体。我们建议开发连接到可调DNA纳米结构上的多价适体，其特异性结合效应细胞和肿瘤细胞，从而能够参与它们的相互作用，这将触发免疫效应细胞的激活以促进肿瘤细胞的破坏。我们将专注于构建连接在DNA纳米支架上的多价和多特异性适体，以指导自然杀伤（NK）细胞攻击肿瘤细胞。这将通过将可编程DNA纳米支架的合理设计与适体文库的系统选择相结合来实现。此外，DNA-纳米结构平台的可扩展特征使得可以并入额外的免疫调节配体以协调和协同针对癌细胞的各种宿主免疫线，包括体液和细胞免疫应答。因此，这些适配体DNA纳米结构可以潜在地用作癌症治疗的“神奇子弹”，以及用于其他疾病的治疗剂。 公共卫生关系：我们提出开发一种新的肿瘤杀伤DNA纳米结构，其中多聚体细胞识别适体将组装到可调和可编程的DNA纳米支架上，以使免疫细胞攻击肿瘤细胞。