Measure immune response induced by FUS ablation for pancreatic cancer (add on to pancreatic registry)

Project Name: Measure immune response induced by FUS ablation for pancreatic cancer (add on to pancreatic registry)
Status: Active
Primary Site: University of Oxford
Funded Date: Sep 23, 2020
Funding Period: Sep 23, 2020 - Sep 23, 2022
Funding Program: Immunotherapy
Category: Clinical Research
Amount Awarded: $119,561.48

Abstract

Multimodal treatments have failed to significantly improve survival in pancreatic cancer. Despite demonstrating efficacy in other solid tumours, novel immunotherapies are ineffective in pancreatic cancer. Pancreatic tumours have ability to escape immune detection, possibly due to a lack of tumour antigen priming. Focused ultrasound has been shown to generate an immune response in tumours. Proposed Study: We are undertaking a Phase 1 clinical study of treating 20 patients with locally advanced pancreatic cancers with HIFU therapy. The proposed study will study the effects of HIFU on the systemic immune response against pancreatic cancer. Methods: Peripheral immunocyte monitoring: Peripheral blood will be analyzed by flow cytometry to detect key myeloid and lymphoid populations involved in regulating the immune response including macrophages, myeloid-derived suppressor cells, neutrophils, cytotoxic T lymphocytes and regulatory T lymphocytes. Immune monitoring will be performed using validated immune panels (DuraClone IM) provided by Beckman Coulter: IM T cell panel, IM Dentritic cells panel, IM Treg panel. T cell receptor sequencing: To determine whether there is greater clonal expansion of T cells following HIFU, CD8+ T cells will be isolated from peripheral blood samples and analysed by immunoSEQ®. Genomic DNA extracted from isolated T cells will be analysed by multiplexed PCR. This technique allows for simultaneous measurement of tens of thousands of T cell receptor (CDR3s), capturing the full T cell receptor repertoire, including individual clones. Future Studies: Understanding the immune response to focused Ultrasound might allow us to rationalise a combined focused ultrasound and immunotherapy approach for pancreatic cancer.

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