MALT1 Inhibitor Impacts T Cell Activation

Example 3

In addition to antigen receptors in B cells, MALT1 also affects signaling downstream of the TCR. Because of the central role of MALT1 in NF-κB signaling, which has been described to be important in the activation of T cells, we investigated the effects of increasing concentrations of the MALT1 inhibitor on T cell activation in both CLL-derived and healthy T cells. Activation and proliferation upon stimulation with soluble anti-CD3/CD28 antibodies was significantly reduced upon MALT1 inhibition in both CD4 and CD8 T cells (FIG. 3A-C). There appeared to be no difference between CLL patients and healthy donors. Additionally, CD107a (LAMP-1) expression as a parameter for T cell degranulation was reduced upon MALT1 inhibition (FIG. 3D). Furthermore, MALT1 inhibition significantly inhibited IFNγ and TNFα cytokine secretion (FIG. 3E). These results suggest that the MALT1 inhibitor impairs various aspects of in vitro T cell activation, when applied at concentrations >1 μM.