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Abstract #0164

Sustained Tumour Response to Repeated STING Activation Assessed by Diffusion Weighted MRI

Upasana Roy1, Carol Box1, Malin Pedersen1, Jessica K. R. Boult1, Antonio Rullan1, Michael Schmohl2, Mario Amend2, Sebastian Carotta3, Anne Vogt3, Kevin J. Harrington1, and Simon P. Robinson1
1Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom, 2Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany, 3Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria

Synopsis

Keywords: Biology, Models, Methods, Cancer, Biomarker

Motivation: Cancer immunotherapy with cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) agonists aims to generate an immune response by T cell priming, activation and infiltration into the tumour microenvironment leading to cell death.

Goal(s): The clinical development of STING agonists would benefit from imaging biomarkers that inform on intratumoural pharmacodynamics and potentially anti-tumour response.

Approach: Longitudinal diffusion-weighted MRI in a thyroid xenograft model indicated sustained increase in ADC as an imaging biomarker of tumour microenvironment changes following treatment with a STING agonist.

Results: The potential use of MRI as an indicator of early STING pathway related pharmacodynamic effects in situ is demonstrated.

Impact: Increased ADC is a sensitive, clinically-translatable imaging biomarker of tumour response to a STING agonist.

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