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.

荧光纳米钻石(FND)标记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是一种无毒、无限光稳定的纳米材料，很容易与抗体结合，并在近红外光谱区发出荧光。在这个第一阶段的SBIR中，我们将使用小鼠黑色素瘤模型，并概述一个计划，即在免疫治疗期间，当免疫抑制细胞群体进入肿瘤微环境和周围组织时，使用FND对其进行成像。在目标1中，我们将50 nm的FND与识别肿瘤相关巨噬细胞()、髓系来源的抑制细胞(MDSC)和调节性T细胞(T-reg)的抗体偶联。在目标2中，我们将制备细胞、骨髓间充质干细胞和T-reg细胞，并用商品化的荧光抗体用流式细胞仪对其进行鉴定。然后，将使用、MDSC和T-reg来验证我们的抗体-FND偶联物。在目标3中，我们将在体外制备FND标记的细胞、骨髓间充质干细胞和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)抑制剂的黑色素瘤荷瘤小鼠中荧光跟踪这些细胞群。我们还将进行平行研究，我们将通过尾静脉直接注射抗体-FND结合物。我们的结果将为预测免疫治疗的反应提供工具。