A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapy
journal contributionposted on 20.04.2021, 00:41 by J Li, A Wuethrich, AAI Sina, HH Cheng, Y Wang, Andreas BehrenAndreas Behren, PN Mainwaring, M Trau
The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.
The authors acknowledge grants received by our laboratory from the National Breast Cancer Foundation of Australia (CG-12-07) and the ARC DP (160102836 and 210103151). These grants have significantly contributed to the environment to stimulate the research described here. J.L. acknowledges support from the Australian Government Research Training Program Scholarship. A.W. and A.A.I.S. thank the National Health and Medical Research Council for funding (APP1173669 and APP1175047). A.B. is the recipient of a Fellowship from the Victorian Government Department of Health and Human Services acting through the Victorian Cancer Agency. We acknowledge the facilities, and the scientific and technical assistance, of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy and Microanalysis, The University of Queensland. We appreciate to receive the technical and scientific guidance from Queensland node of the Australian National Fabrication Facility (Q-ANFF) in confocal Raman mapping and spectroscopic ellipsometry measurement.
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Science & TechnologyMultidisciplinary SciencesScience & Technology - Other TopicsHumansMelanomaGranulocyte Colony-Stimulating FactorGranulocyte-Macrophage Colony-Stimulating FactorCytokinesMicroscopy, ConfocalMonitoring, ImmunologicImmunotherapySpectrum Analysis, RamanCohort StudiesPilot ProjectsReproducibility of ResultsChemokine CX3CL1IpilimumabImmune Checkpoint Inhibitors