Project 1: Nanoshells Enabled Tumor Ablation and Immunotherapy

项目 1：纳米壳实现肿瘤消融和免疫治疗

• 批准号: 9043695
• 负责人: Natalie Allen Gude
• 金额: $ 14.05万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-29 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9043695
• 关键词: 4T1; Ablation; Adjuvant; Agonist; Antigen-Presenting Cells; Attenuated; Breast Cancer Model; Breast Melanoma; CT26; Cancer Model; Colon; Colon Carcinoma; Comprehensive Cancer Center; Coupled; Coupling; Data; Disease; Distal; Education; Environment; Focused Ultrasound Therapy; Gases; Goals; Immune; Immune response; Immune system; Immunity; Immunologic Adjuvants; Immunotherapy; In Vitro; Inflammatory Response; Lead; Learning; Malignant Neoplasms; Mechanics; Memory; Modality; Modeling; Mus; Neoplasm Metastasis; Outcome; Property; Proteins; Research; Science; Scientist; Silicon Dioxide; Site; Students; Surface; TLR7 gene; Testing; Training; Tumor Antigens; Tumor Tissue; Underrepresented Students; Work; abstracting; base; cancer immunotherapy; cancer therapy; career; collaborative environment; immunogenicity; improved; in vivo; insight; malignant breast neoplasm; melanoma; mouse model; nanoshell; neoplasm immunotherapy; neoplastic cell; response; skills; therapy outcome; tumor; tumor ablation; tumor growth

Abstract Studies have indicated that ablative therapies may augment the host immune system response against tumor antigens by enhancing the local immunogenicity of the ablated tumor as well as distal metastatic sites thereby improving therapy outcomes. The proposed project aims to evaluate the synergy of mechanical HIFU using gas filled silica nanoshells in combination with an immune adjuvant, a TLR7 agonist, which will be conjugated to the surface of silica nanoshells. It is postulated that applying mechanical HIFU to the tumor will condition the tumor tissue environment by exposing tumor antigens without denaturing the proteins and by initiating an inflammatory response. Preliminary studies have shown that the immunostimulatory properties of a TLR7 agonist are enhanced when conjugated to 100nm silica nanoshells. These nanoshell conjugates will be used as an immune adjuvant in order to enhance the antitumor immune response. Combination of HIFU ablative therapy and an immune adjuvant will be investigated in a metastatic colon and breast cancer murine model with the aim to enhance tumor ablation, reduce tumor growth, and to elicit a systemic antitumor immune response. The partnership will be used as a mean to support students underrepresented in science to become young independent scientists. The project will provide many opportunities to promote a learning and collaborative environment for students in research education. This will aid students to develop technical and interpersonal skills which will assist them in fulfilling a successful career.

摘要 研究表明，消融治疗可以增强宿主免疫系统对肿瘤的反应 通过增强消融的肿瘤以及远端转移位点的局部免疫原性， 改善治疗效果。拟议的项目旨在评估机械HIFU的协同作用， 气体填充的二氧化硅纳米壳与免疫佐剂、TLR7激动剂组合，其将被缀合 到二氧化硅纳米壳的表面。据推测，将机械HIFU应用于肿瘤将调节肿瘤的生长。 通过暴露肿瘤抗原而不使蛋白质变性，并通过引发肿瘤抗原的释放， 炎症反应。初步研究表明，TLR7的免疫刺激特性 当与100 nm二氧化硅纳米壳缀合时，激动剂增强。将使用这些纳米壳缀合物 作为免疫佐剂以增强抗肿瘤免疫应答。HIFU消融组合 将在转移性结肠癌和乳腺癌小鼠模型中研究治疗和免疫佐剂 目的是增强肿瘤消融，减少肿瘤生长，并引发全身抗肿瘤免疫， 反应该伙伴关系将被用作一种手段，以支持在科学中代表性不足的学生成为 年轻的独立科学家该项目将提供许多机会，促进学习和 研究性教育中的学生协作环境。这将有助于学生发展技术和 人际交往能力，这将有助于他们实现成功的职业生涯。