Topic 396 - Imaging for Cancer Immunotherapies-Moonshot

主题 396 - 癌症免疫疗法的成像 - Moonshot

• 批准号: 10022349
• 负责人: Arfaan Rampersaud
• 金额: $ 30万
• 依托单位: COLUMBUS NANOWORKS, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2020-06-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10022349
• 关键词: Antibodies; Antigens; Cells; Flow Cytometry; Fluorescence; Fluorescent Antibody Technique; Harvest; Image; Immune; Immunologic Monitoring; Immunosuppressive Agents; Immunotherapy; In Vitro; Inbred BALB C Mice; Label; Melanoma Cell; Modeling; Mus; Myeloid-derived suppressor cells; PDCD1LG1 gene; Peripheral; Phase; Placebos; Population; Regulatory T-Lymphocyte; Small Business Innovation Research Grant; Suppressor-Effector T-Lymphocytes; Tail; Testing; Tissues; Tumor-associated macrophages; Veins; anti-PD-L1; base; cancer imaging; cancer immunotherapy; cellular imaging; imaging study; in vivo; in vivo imaging; inhibitor/antagonist; melanoma; nanodiamond; nanomaterials; predicting response; predictive tools; prognostic; recruit; treatment response; tumor; tumor microenvironment

In vivo imaging of cells labeled with fluorescent nanodiamonds (FNDs) is a new way of monitoring immune cells during cancer immunotherapy. FNDs are non-toxic, infinitely photostable nanomaterials that are easily conjugated with antibodies, and emit fluorescence in the near infrared spectral region. In this Phase I SBIR, we will use a murine melanoma model and outline a plan to use FNDs for imaging immunosupressive cell populations as they enter the tumor microenvironment and peripheral tissues during immunotherapy. In Objective 1, we will conjugate 50 nm FNDs with antibodies that recognize tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (T-reg). In Objective 2, we will prepare TAM, MDSC and T-reg cells and characterize them by flow cytometry using commercial fluorescent antibodies. The TAM, MDSC and T-reg will then be used to validate our antibody-FND conjugates. In Objective 3, we will prepare FND-labeled TAM, MDSC and T-reg cells ex vivo and fluorescently track these cell populations in melanoma-bearing mice receiving placebo or mouse anti-PD-L1 antibody (programmed death ligand 1) inhibitor. We will also perform parallel studies where we image antibody-FND conjugates that are directly injected through the tail-vein. Our results will provide tools for predicting the response to immunotherapy.

用荧光纳米金刚石（FND）标记的细胞的体内成像是在癌症免疫治疗过程中监测免疫细胞的一种新方法。 FND 是无毒、无限光稳定的纳米材料，很容易与抗体结合，并在近红外光谱区域发射荧光。在此 I 期 SBIR 中，我们将使用小鼠黑色素瘤模型，并概述一项计划，利用 FND 对免疫抑制细胞群在免疫治疗期间进入肿瘤微环境和外周组织时进行成像。在目标 1 中，我们将 50 nm FND 与识别肿瘤相关巨噬细胞 (TAM)、骨髓源性抑制细胞 (MDSC) 和调节性 T 细胞 (T-reg) 的抗体结合。在目标 2 中，我们将制备 TAM、MDSC 和 T-reg 细胞，并使用商业荧光抗体通过流式细胞术对其进行表征。然后，TAM、MDSC 和 T-reg 将用于验证我们的抗体-FND 缀合物。在目标 3 中，我们将离体制备 FND 标记的 TAM、MDSC 和 T-reg 细胞，并在接受安慰剂或小鼠抗 PD-L1 抗体（程序性死亡配体 1）抑制剂的黑色素瘤小鼠中荧光追踪这些细胞群。我们还将进行平行研究，对直接通过尾静脉注射的抗体-FND 缀合物进行成像。我们的结果将为预测免疫疗法的反应提供工具。