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

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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.