Oclacitinib depletes canine CD4+ and CD8+ T cells in vitro

Treatment of canine cutaneous epitheliotropic T‐cell lymphoma with oclacitinib: a case report

“…The positive effect of oclacitinib may have been due to direct inhibition of T-cell proliferation, induction of T-cell apoptosis, anti-IL-15 effects or inhibition of upregulated JAK/STAT signalling. [5][6][7][8][9][10] Although the duration of disease control was short (three months), this was comparable to other common treatment protocols and treatment with oclacitinib was well-tolerated with no adverse effects. Signs of the disease had been present for six months before presentation so it is possible that a better outcome could be seen in earlier cases.…”

“…4 The JAK/STAT pathways are essential for T-cell function, and oclacitinib has been shown to deplete canine CD4+ and CD8+ T cells, and cause apoptosis of CD4+ and CD8+ T cells in vitro. 5 cell proliferation and cytokine production in vitro, yet this was only severe and significant at a concentration corresponding to an oral dose of 3-4 mg/kg twice daily and did not appear to be significant at the usual therapeutic concentration. 6 In humans, alterations in JAK/STAT signalling have been described in most T-cell lymphoproliferative disorders including CETL.…”

Oclacitinib, a Janus Kinase Inhibitor, Reduces the Frequency of IL-4- and IL-10-, but Not IFN-γ-, Producing Murine CD4+ and CD8+ T Cells and Counteracts the Induction of Type 1 Regulatory T Cells

“…This work is a continuation of our research [ 29 ] on an influence of OCL on T cells, which was conducted on canine peripheral blood mononuclear cells (PBMCs), i.e., on cells of the target species for which the drug (APOQUEL) has been specifically approved. In order to achieve research objectives formulated in this paper, the present study by necessity was conducted on mouse lymphocytes because anti-canine monoclonal antibodies for flow cytometric detection of Tr1 cells and intracellular cytokine production as well as to obtain effective stimulation of cells (to induce cell proliferation and cytokine synthesis) are still not available for dogs.…”

“…This was not unexpected since Tr1 cells represent an inducible regulatory cells which are generated from naïve CD4 + T cells under conditions involving T cell activation [ 39 ], as was the case in the present studies. In our previous research it was found that OCL inhibited activation of CD4 + T cells [ 29 ]. What is more, the findings of certain studies indicate that generation of Tr1 cells can depend on STAT3 activation [ 40 , 41 ].…”

“…However, it does not preclude a negative effect of the drug on Th1 cells. In our previous studies conducted on non-stimulated canine PBMCs, we found that OCL exerted a proapoptotic effect on CD4 + and CD8 + T cells and caused depletion of these cells [ 29 ].…”