The advent and clinical success of immune checkpoint inhibitors Ipilimumab, Nivolumab and Pembrolizumab has had a seismic impact on our drug discovery focus and rationale. Novel extrinsic targets that enhance immune responses to cancer are actively being pursued, while tumor intrinsic targets that render cancer cells more sensitive to the immune system have joined traditional intrinsic targets (e.g. directly cytotoxic) in the drug discovery pipeline. The phosphatase PTPN2 (TC-PTP) and its paralog PTPN1 (PTP-1B) are negative regulators of several cytokine signaling pathways and T cell receptor (TCR) signaling. In a recent publication, Baumgartner et al. demonstrate the pre-clinical efficacy of a first-in-class dual PTPN1/N2 active site inhibitor (ABBV-CLS-484/AC484) in cancer models.
Keywords: CD8 T cells; IFNg; cancer immunotherapy; cytokine receptors; phosphatases.
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