Journal article
A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity
S Liang, E Tran, X Du, J Dong, H Sudholz, H Chen, Z Qu, ND Huntington, JJ Babon, NJ Kershaw, ZY Zhang, JB Baell, F Wiede, T Tiganis
Nature Communications | Published : 2023
Abstract
The inhibition of protein tyrosine phosphatases 1B (PTP1B) and N2 (PTPN2) has emerged as an exciting approach for bolstering T cell anti-tumor immunity. ABBV-CLS-484 is a PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. Here we have explored the therapeutic potential of a related small-molecule-inhibitor, Compound-182. We demonstrate that Compound-182 is a highly potent and selective active site competitive inhibitor of PTP1B and PTPN2 that enhances T cell recruitment and activation and represses the growth of tumors in mice, without promoting overt immune-related toxicities. The enhanced anti-tumor immunity in immunogenic tumors can be ascribed to the inhibition of PTP1B/PTPN2 in ..
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Awarded by Australian Cancer Research Foundation
Funding Acknowledgements
We thank Crystal Stivala for her technical support. This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (2008572 to T.T.; 1184615 to N.D.H. and T.T.), the US Army Department of Defense (W81XWH-21-1-0126 BC200609 to T.T.), and the US National Institutes of Health (RO1CA069202 to Z.-Y.Z.).~This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the Australian Cancer Research Foundation (ACRF) Eiger.