SBIR PHASE I TOPIC 396 EVALUATION OF [18F]F-ARAG, A T CELL-SPECIFIC PET AGENT, AS AN IMAGING BIOMARKER PREDICTIVE OF RESPONSE TO IMMUNOTHERAPIES - MOONSHOT

SBIR 第一阶段主题 396 评估 [18F]F-ARAG（一种 T 细胞特异性 PET 制剂）作为预测免疫治疗反应的成像生物标志物 - Moonshot

• 批准号: 10013724
• 负责人: JELENA LEVI
• 金额: $ 30万
• 依托单位: CELLSIGHT TECHNOLOGIES, 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/10013724
• 关键词: Address; Agonist; Antigen-Antibody Complex; CD8-Positive T-Lymphocytes; Combination immunotherapy; Development; Evaluation; Image; Immune; Immune response; Immunooncology; Immunotherapy; Methods; Patient Selection; Patients; Phase; Poly I-C; Poly ICLC; Positron-Emission Tomography; Process; SLEB2 gene; Scanning; Small Business Innovation Research Grant; Solid Neoplasm; T-Lymphocyte; TLR3 gene; Tumor-infiltrating immune cells; anti-PD-1; cancer therapy; combinatorial; imaging biomarker; improved; inhibitor/antagonist; novel; pre-clinical; predicting response; responders and non-responders; response

Immunotherapy radically transformed cancer treatment, but only a fraction of patients with advanced solid tumors achieves a durable response to therapy. Compelling evidence points to intratumoral CD8+ T cell infiltration as a critical component of a successful immunotherapy. However, there are currently no noninvasive methods capable of evaluating immune contexture prior to or during immunotherapy. Our inability to non-invasively assess patients’ immune milieu represents a major bottleneck for the development of more effective immunotherapies. To address the urgent need for a non-invasive immunomonitoring method, we are proposing to investigate a PET agent specific for activated T-cells, [18F]F-AraG, as an imaging biomarker predictive of response to mono and combinatorial immunotherapy. In this preclinical project, we will: 1) use [18F]F-AraG to differentiate between responders and non-responders undergoing PD-1 treatment; 2) use [18F]F-AraG to differentiate between responders and non-responders undergoing combinatorial PD-1/poly IC LC treatment and 3) define factors relating to [18F]F-AraG scan that are indicative of an adequate immune response. By using a T cell-specific agent we anticipate gaining a better understanding of the complex immunological processes necessary for a successful immunotherapy. This imaging strategy could improve many facets of immunooncology – from development of novel combinatorial approaches to patient selection and management.

免疫疗法从根本上改变了癌症治疗，但只有一小部分晚期实体瘤患者对治疗产生了持久的反应。令人信服的证据表明，肿瘤内CD 8 + T细胞浸润是成功免疫治疗的关键组成部分。然而，目前还没有能够在免疫治疗之前或期间评估免疫结构的非侵入性方法。我们无法非侵入性地评估患者的免疫环境，这是开发更有效的免疫疗法的主要瓶颈。为了解决对非侵入性免疫监测方法的迫切需求，我们建议研究对活化T细胞特异性的PET试剂，[18 F]F-AraG，作为预测对单一和组合免疫疗法的响应的成像生物标志物。在该临床前项目中，我们将：1）使用[18F]F-AraG来区分接受PD-1治疗的应答者和非应答者; 2）使用[18F]F-AraG来区分接受组合PD-1/聚IC LC治疗的应答者和非应答者;和3）定义与指示充分免疫应答的[18F]F-AraG扫描相关的因素。通过使用T细胞特异性试剂，我们预计将更好地了解成功免疫治疗所需的复杂免疫过程。这种成像策略可以改善免疫肿瘤学的许多方面-从开发新的组合方法到患者选择和管理。