A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity

• DOI: 10.1038/s41467-023-40170-8
• Publication Date: 2023-07-27T12:04:50Z
• Authors: Shuwei Liang; Eric Tran; Xin Du; Jiajun Dong; Harrison Sudholz; Hao Chen; Zihan Qu; Nicholas D. Hunti...; Jeffrey J. Babon; Nadia J. Kershaw; Zhong-Yin Zhang; Jonathan B. Baell; Florian Wiede; Tony Tiganis
• Keywords: Protein Tyrosine Phosphatase, Non-Receptor Type 1; Mice; Protein Tyrosine Phosphatase, Non-Receptor Type 2; Science; Neoplasms; T-Lymphocytes; Q; Animals; Enzyme Inhibitors; Article; Phosphoric Monoester Hydrolases; 3. Good health

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 solid tumors. Here we have explored the therapeutic potential related small-molecule-inhibitor, Compound-182. We demonstrate that Compound-182 highly potent selective active site competitive PTP1B PTPN2 enhances recruitment activation represses growth tumors mice, without promoting overt immune-related toxicities. enhanced immunity immunogenic can be ascribed to cells, whereas cold tumors, elicited direct effects on both tumor cells cells. Importantly, treatment with rendered otherwise resistant sensitive α-PD-1 therapy. Our findings establish small molecule inhibitors enhance combat cancer.