Fig. 6: Panobinostat upregulates CD38 expression on H9 CTCL cells and enhances survival in a mouse model of CTCL in combination with αCD38 antibody immunotherapy. | Leukemia

Fig. 6: Panobinostat upregulates CD38 expression on H9 CTCL cells and enhances survival in a mouse model of CTCL in combination with αCD38 antibody immunotherapy.

From: CD38 in the pathobiology of cutaneous T-cell lymphoma and the potential for combination therapeutic intervention

Fig. 6

A CTCL cells were treated with one of several histone deacetylase inhibitor agents followed by staining for CD38 and subsequent analysis via flow cytometry using a BD LSRFortessa (figure made with Biorender). B The mean fluorescent intensity of CD38 expression on CTCL cells treated for 72 h with either 1 μM vorinostat, 1 nM romidepsin, 25 nM of panobinostat, or DMSO control (panobinostat vs DMSO p < 0.001 by unpaired t test). C Representative histograms displaying CD38 expression at 72 h for increasing doses of panobinostat (5 nM, 10 nM, and 25 nM) compared to an isotype control. D Median fluorescence intensity (MFI) of CD38 expression on H9 cells treated with increasing doses of panobinostat for across multiple time points (24 h, 48 h, and 72 h) (max 85% increase in CD38 expression with 25 nM panobinostat vs. DMSO at 72 h; p < 0.0001 by 2way ANOVA). E Experimental design and treatment regimen for the in vivo combination αCD38 antibody and panobinostat in mice engrafted H9 luciferase CTCL cells. The animals were divided into four age and sex-matched experimental groups (N = 4 for all groups): Vehicle and IgG; Vehicle and αCD38 antibody; Panobinostat and IgG; and Panobinostat and αCD38 antibody. Panobinostat (20 mg/kg) and vehicle (2% DMSO, 48% PEG300, 2% Tween80, and 48% ddH2O) were administered via IP injection twice a week, while αCD38 antibody (daratumumab 100 mg/kg) and IgG isotype control (0.8 mg/kg) were administered subcutaneously once a week for three weeks. Mice were monitored and survival was tracked (figure made with Biorender). F Survival curve depicting the outcomes of the four experimental groups in the αCD38 antibody and panobinostat combination study (vehicle/IgG median survival 23 days; vehicle/ αCD38 antibody median survival 32 days; Panobinostat/IgG median survival 27.5 days; combination median survival 39 days; p = 0.01 by log-rank test).

Back to article page