TY - JOUR
T1 - A digital single-molecule nanopillar SERS platform for predicting and monitoring immune toxicities in immunotherapy
AU - Li, Junrong
AU - Wuethrich, Alain
AU - Sina, Abu A. I.
AU - Cheng, Han-Hao
AU - Wang, Yuling
AU - Behren, Andreas
AU - Mainwaring, Paul N.
AU - Trau, Matt
N1 - Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2021/2/17
Y1 - 2021/2/17
N2 - 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.
AB - 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.
UR - http://purl.org/au-research/grants/arc/DP160102836
UR - http://purl.org/au-research/grants/arc/
UR - http://purl.org/au-research/grants/nhmrc/1175047
UR - http://purl.org/au-research/grants/nhmrc/1173669
UR - http://www.scopus.com/inward/record.url?scp=85101087056&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-21431-w
DO - 10.1038/s41467-021-21431-w
M3 - Article
C2 - 33597530
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1087
ER -