A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapy

Junrong Li, Alain Wuethrich (), Abu A. I. Sina, Han-Hao Cheng, Yuling Wang (), Andreas Behren, Paul N. Mainwaring and Matt Trau ()
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Junrong Li: The University of Queensland
Alain Wuethrich: The University of Queensland
Abu A. I. Sina: The University of Queensland
Han-Hao Cheng: The University of Queensland
Yuling Wang: Macquarie University
Andreas Behren: La Trobe University
Paul N. Mainwaring: The University of Queensland
Matt Trau: The University of Queensland

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-21431-w

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