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Comment
. 2024 Jan;102(1):8-11.
doi: 10.1111/imcb.12711. Epub 2023 Nov 19.

Small molecule. Big biology. Dual phosphatase inhibitor enters the immunotherapy fray

Nicholas S Wilson  1 , Nicholas D Huntington  2
Affiliations
Comment

Small molecule. Big biology. Dual phosphatase inhibitor enters the immunotherapy fray

Nicholas S Wilson et al. Immunol Cell Biol. 2024 Jan.

Abstract

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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Comment on

  • The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity.
    Baumgartner CK, Ebrahimi-Nik H, Iracheta-Vellve A, Hamel KM, Olander KE, Davis TGR, McGuire KA, Halvorsen GT, Avila OI, Patel CH, Kim SY, Kammula AV, Muscato AJ, Halliwill K, Geda P, Klinge KL, Xiong Z, Duggan R, Mu L, Yeary MD, Patti JC, Balon TM, Mathew R, Backus C, Kennedy DE, Chen A, Longenecker K, Klahn JT, Hrusch CL, Krishnan N, Hutchins CW, Dunning JP, Bulic M, Tiwari P, Colvin KJ, Chuong CL, Kohnle IC, Rees MG, Boghossian A, Ronan M, Roth JA, Wu MJ, Suermondt JSMT, Knudsen NH, Cheruiyot CK, Sen DR, Griffin GK, Golub TR, El-Bardeesy N, Decker JH, Yang Y, Guffroy M, Fossey S, Trusk P, Sun IM, Liu Y, Qiu W, Sun Q, Paddock MN, Farney EP, Matulenko MA, Beauregard C, Frost JM, Yates KB, Kym PR, Manguso RT. Baumgartner CK, et al. Nature. 2023 Oct;622(7984):850-862. doi: 10.1038/s41586-023-06575-7. Epub 2023 Oct 4. Nature. 2023. PMID: 37794185 Free PMC article.

References

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