Urinary detection of early responses to checkpoint blockade and of resistance to it via protease-cleaved antibody-conjugated sensors.
Urinary detection of early responses to checkpoint blockade and of resistance to it via protease-cleaved antibody-conjugated sensors.
复制标题
通过蛋白酶切割的抗体偶联传感器，通过尿液检测对检查点封锁的早期反应和对其耐药性。
DOI：
10.1038/s41551-022-00852-y
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发表时间：
2022-03
影响因子：
28.1
通讯作者：
Kwong GA
中科院分区：
文献类型：
--
作者：
Mac QD;Sivakumar A;Phuengkham H;Xu C;Bowen JR;Su FY;Stentz SZ;Sim H;Harris AM;Li TT;Qiu P;Kwong GA
Immune checkpoint blockade (ICB) therapy does not benefit the majority of treated patients, and those who respond to the therapy can become resistant to it. Here we report the design and performance of systemically administered activity sensors conjugated to anti-programmed cell death protein 1 (αPD1) antibodies for the monitoring of antitumour responses to ICB therapy. The sensors consist of a library of mass-barcoded protease substrates that, when cleaved by tumour and immune proteases, are released into urine, where they can be detected by mass spectrometry. By using syngeneic mouse models of colorectal cancer, we show that random-forest classification trained on mass-spectrometry signatures from a library of αPD1-conjugated mass-barcoded activity sensors for differentially expressed tumour and immune proteases can be used to detect early antitumour responses and to discriminate resistance to ICB therapy driven by loss-of-function mutations in either the B2m or Jak1 genes. Our data supports the use of activity-based biomarkers for early on-treatment response assessment and classification of refractory tumours based on resistance mechanisms. A library of systemically administered protease-cleavable sensors conjugated to anti-programmed cell death protein 1 antibodies allows for the early urinary detection and monitoring of antitumour responses to immune checkpoint blockade therapy in mice.
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影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
82.9
作者：
Fairfax BP;Taylor CA;Watson RA;Nassiri I;Danielli S;Fang H;Mahé EA;Cooper R;Woodcock V;Traill Z;Al-Mossawi MH;Knight JC;Klenerman P;Payne M;Middleton MR
通讯作者：
Middleton MR
影响因子：
3.3
作者：
Arlot, Sylvain;Celisse, Alain
通讯作者：
Celisse, Alain
影响因子：
5.7
作者：
Austin, Richard J.;Lemon, Bryan D.;Wesche, Holger
通讯作者：
Wesche, Holger
影响因子：
22.7
作者：
Bratman, Scott V.;Yang, S. Y. Cindy;Pugh, Trevor J.
通讯作者：
Pugh, Trevor J.