Mepazine/Biperiden
Mepazine is a phenothiazine antipsychotic medication. Biperiden is a medication used to treat Parkinson’s disease and is a synthetic acetylcholine antagonist. Both of these drugs inhibit MALT1, which is associated with the CBM signalosome complex. Pilato, et al. published an article in Nature Research; Oct 2018 titled “Targeting the CBM Complex Causes Treg Cells to Prime Tumours for Immune Checkpoint Therapy.” They demonstrated that using Mepazine to inhibit MALT1 could help convert immunologically cold tumors to hot ones. In the animal model, they showed the combination of Mepazine with PD-1 inhibitors causes the development of an anti-cancer immune response with relapse-free tumor control in a model that does not respond to PD-1 therapy alone. This is important, as the majority of cancers do not respond to PD-1 therapy due to a lack of infiltration of attacking immune cells and a predominance of tumor-protecting regulatory immune cells. They also showed that MALT1 inhibition could actually convert regulatory cells into ones that are more tumor-attacking. The big advantage here is that most strategies are to decrease regulatory cells, generally by killing them. This drug may be able to make good use of those regulatory cells in the tumor environment to convert them into attacking the tumor.
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