Journal article
Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a JAK1/JAK2 inhibitor
T Ge, AL Phung, G Jhala, P Trivedi, N Principe, DJ De George, EG Pappas, S Litwak, L Sanz-Villanueva, T Catterall, S Fynch, L Boon, TW Kay, J Chee, B Krishnamurthy, HE Thomas
Clinical and Translational Immunology | Published : 2022
DOI: 10.1002/cti2.1425
Open access
Abstract
Objectives: Immune checkpoint inhibitors have achieved clinical success in cancer treatment, but this treatment causes immune-related adverse events, including type 1 diabetes (T1D). Our aim was to test whether a JAK1/JAK2 inhibitor, effective at treating spontaneous autoimmune diabetes in nonobese diabetic (NOD) mice, can prevent diabetes secondary to PD-L1 blockade. Methods: Anti-PD-L1 antibody was injected into NOD mice to induce diabetes, and JAK1/JAK2 inhibitor LN3103801 was administered by oral gavage to prevent diabetes. Flow cytometry was used to study T cells and beta cells. Mesothelioma cells were inoculated into BALB/c mice to induce a transplantable tumour model. Results: Anti-PD..
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Awarded by U.S. Department of Defense
Funding Acknowledgements
This work is supported by the National Health and Medical Research Council of Australia (NHMRC) Program grant (GNT1150425) and the Diabetes Australia Research Program. The St Vincent's Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria. JC, AP and NP received support from the UWA Raine Foundation, Mesothelioma Applied Research Foundation and the US Department of Defence. JC and NP were funded by fellowships and scholarships from Cancer Council Western Australia and icare NSW Dust Diseases Board.