Development of a Longitudinal Molecular Imaging Platform to Support Immuno-Oncology Research

Abstract Immunotherapy is one of the most promising new cancer treatment approachesWhile some patients experience astounding results in long term remission rates and eradication of metastatic growthsthe number of responders is surprisingly lowDue to the large number of coincident factors and cell typesthe predominant way that researchers study tumors and their responses to immunotherapies is through ex vivo analysessuch as histology or flow cytometryUnfortunatelythese techniques preclude longitudinal studies because the tissue must be excisedmaking it very challenging to study the dynamic nature of the tumor over time and resulting in a slow and costly research pipelineWhile noninvasive imaging technologies existmultiplexing several tumor readouts is either not possible or requires a highly complex workflowTo address this needSonoVol is proposing to build and validate a novel preclinical molecular imaging platformcapable of multiplexing several parameters of interestmultiple T cell subtypestumor cellsetcwithD tomographic imagingThe system will leverage ultrasound photoacousticUSPAimaging in combination with a novel genetic reporterbacterial phytochrome photoreceptorsBphPBphPs are a class of proteins that exhibit near infraredNIRabsorbance and fluorescence and are red shifted relative to any other phytochromesmaking them ideal for in vivo imaging at depthAdditionallyBphPs experience pronounced conformational changes upon photoisomerizationenabling photo control andconsequentlyhighly sensitive cell trackingtens to hundreds of cells at depthBy commercializing this imaging reporter biotechnology within the SonoVol VegaTMwe will enable researchers to perform mechanistic studies of tumor microenvironment and accelerate translation of critical immunotherapies to the clinicThis work will proceed in three stagesFirstwe will deploy new software modules that enable pushbutton PA BphP imaging on the VegaSecondwe will prepare and verify two distinct BphP labelled cellsmurine prostate tumor cells and CDT cellsFinallywe will perform a validation of our imaging system using adoptive transfer and observe T cell infiltration into tumors under two immunotherapy conditionsanti PDLtherapy aloneand a combination therapy shown to enhance T cell traffickinganti PDLplus radiationProject Narrative Immunotherapy is a groundbreaking treatment that uses the body s own immune system to help fight cancerhowevermany cancers are resistant to this type of therapy and researchers do not fully understand whyTo understand the biological reasons why some cancers respondand others do notscientists need new noninvasive imaging tools to observe how immune cells move in and out of a tumorSonoVolIncis proposing to develop a benchtop instrument that can track multiple tumor and immune cell types in rodentsWith this technologynew insights into the biology of cancer can be gleaned in order to improve the effectiveness of immunotherapyand speed these therapiestranslation to the clinic