AACR Annual meeting 2021 Identification of Tofacitinib, and on experimental Sjögren’s syndrome model in mice 1036

Ruiqing Yan, Yanping Yuan, Chao Luo,Chuanzhi Yangmeng, Li Fang, Qing Lin Oncology and Unit, WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.

Background Results Compared with vehicle group, mice in Tofacitinib, Filgotinib and In addition, Tofacitinib, Filgotinib and Ruxolitinib also Ruxolitinib group exhibited a less ANA autoantibody in both saliva reduced the percentage of circulted Th1/Th17 cells in the Sjögren’s syndrome, which is affected hundreds of millions After three weeks of JAKs treatment, mice in Tofacitinib, Filgotinib and serum. blood of ESS mice. of people worldwide, is a chronic autoimmune disorder and Ruxolitinib were markedly increased saliva flow when compared ANA in saliva characterized by leukocytic infiltration into the exocrine ANA in serum with those in vehicle group. 1500 glands, such as the salivary and lacrimal glands. However, 8000 25

the pathological mechanism remains to be elucidated, and ）

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urgent need for the novel treatment should still meet. Over m

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offers us an invaluable tool to understand SjS pathogenesis i

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l 15 treatment. a S 0 0 In this study, we identified the potential effect of l l a le ib ib ib a le ib ib ib rm ic in in in m ic n n n Tofacitinib, Filgotinib and Ruxolitinib on the experimental h t it it r ti ti ti 10 o e o l c o h o li i N V g o a N e g o c il x f V il x fa Sjögren’s syndrome model in C57/B6L mice from both In- 0 7 4 1 8 5 F u o F u o 1 2 2 3 R T R T life study and ex-vivo study at the endpoint. Our data suggest Days Figure 3 The effect of three JAK inhibitors on reducing the autoantibody that Tofacitinib, Filgotinib and Ruxolitinib, three JAK against ANA in both saliva and serum inhibtors exhibits the effect on reducing the severity of Figure 1 The effect of three JAK inhibitors on Saliva flow rate Sjögren’s syndrome in mice, reduces autoantibodies Furtherly, Tofacitinib, Filgotinib and Ruxolitinib reduced the producion and promotes the saliva secretion in mice, which Compared with vehicle group, mice in Tofacitinib, Filgotinib and percentage of Th1/Th17 cells in the spleen of ESS mice. also provides the direction of novel JAK inhibitor on Ruxolitinib group showed a less release of against the treatment for Sjögren’s syndrome. dsDNA and M3R into blood.

Methods -dsDNA in serum M3R in serum 600 200000

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The ESS model was induced in C57/B6L mice with SG m

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by homogenized for bilateral SG of 8-week-old C57BL/6 i

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a measured by BCA, added to the same volume of Freund’s a Summary complete adjuvant and emulsified to 4 mg/mL. On day 0, 0 0 l l a e the emulsion was subcutaneously injected into the back of a le ib ib ib l ib ib ib m ic n n n m ic n in in In the present study, we found that JAKs inhigtors r ti ti ti r h ti t t o h o li i o e o li i the 8-week-old mice, and this operation was repeated on N e g o c N g o c V il x fa V il x fa (Tofacitinib, Filgotinib and Ruxolitinib) improved the saliva F u o F u o day 7. On the 14th day, an equal volume of Freund’s R T R T flow of ESS mice, and inhibited the release of autoantibodies incomplete adjuvant was mixed with SG to form an including those against for dsDNA, M3R and ANA. In emulsion of the same concentration to boost immunity and addition, Tofacitinib, Filgotinib and Ruxolitinib reduced the injected in the same way. presense of Th1/Th17 cells in both spleen and blood of ESS Figure 2 The effect of three JAK inhibitors on reducing the Figure 4 The effect of three JAK inhibitors on reducing the presense of mice. In all, the JAKs inhibitor potentially improve the autoantibody against dsDNA and M3R in serum Th1/Th17 cell in spleen syndrome of ESS mice.