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

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CD8+ 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环境的无创方法。我们无法无创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，我们建议研究一种针对活化t细胞的PET剂[18F]F-AraG，作为预测对单一和联合免疫治疗反应的成像生物标志物。在本临床前项目中，我们将：1)使用[18F]F-AraG来区分PD-1治疗的应答者和无应答者；2)使用[18F]F-AraG来区分PD-1/poly IC LC联合治疗的应答者和无应答者；3)定义与[18F]F-AraG扫描相关的因素，这些因素表明免疫应答充分。通过使用T细胞特异性药物，我们期望对成功的免疫治疗所必需的复杂免疫过程有更好的了解。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的选择和管理。

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.