Lausanne: Development of new immunomodulatory drugs

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Scientists at Lausanne University have shed light on the molecular function of MALT1, an enzyme downstream of the antigen receptor, controlling T- and B- cell function.

Triggering of the antigen T- and B-cell receptor leads to the initiation of multiple signalling pathways that regulate cellular proliferation, survival and effector function of T- and B-cells. Deregulation of lymphocyte activation may lead to lymphomas, inflammatory or autoimmune diseases.

The technology provides means, such as enzyme assays or screening methods, that make it possible to the test or screen for compounds that interfere in a signalling pathway regulating T- or B-cell function.

The scientists have identified MALT1 proteolytic activity and described how MALT1 inhibition in lymphocytes results in impaired antigen receptor-induced activation of the transcription factor NF-kB and, as a consequence, impaired proliferation and cytokine production.

In addition, they have demonstrated activity of MALT1 in cell lines derived from a subtype of diffuse large B-cell lymphoma, suggesting that the newly identified MALT1 enzymatic activity is implicated in the development of this disease.

From this it follows that therapeutic targeting of the protease activity of MALT1 may be a useful approach for the treatment of autoimmune or inflammatory diseases, for the prevention of transplant rejection and the treatment of lymphomas. It may lead to the development of an innovative drug, targeting a newly identified key pathway controlling lymphocyte function.