ArticleFrontiers in immunology2020
Pharmacological Inhibition of MALT1 Protease Leads to a Progressive IPEX-Like Pathology.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- MALT1 alternative splicing-A molecular rheostat for balancing immune activation and homeostasis.Science advances · 2026Article
- MALT1 protease inhibition restrains glioblastoma progression by reversing tumor-associated macrophage-dependent immunosuppression in mice.Nature communications · 2026Article
- Preventing MALT1-mediated CYLD cleavage induces intestinal dysbiosis and reduces EAE severity.EMBO reports · 2026Article
- Therapeutic targeting of MALT1 in oncology: Mechanism, inhibitor development, and clinical prospects.Journal of cell communication and signaling · 2026Review
- Running on Empty Signals: What Human MALT1 Deficiency Reveals About Immune Control.Journal of immunology research · 2026Review
- A small-molecule inhibitor of BCL10-MALT1 interaction abrogates progression of diffuse large B cell lymphoma.The Journal of clinical investigation · 2025Article
- Deciphering the role of the MALT1-RC3H1 axis in regulating GPX4 protein stability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation.The Biochemical journal · 2024Article
- The state of the art in secondary pharmacology and its impact on the safety of new medicines.Nature reviews. Drug discovery · 2024Review
- Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1?Biochemical pharmacology · 2023Review
- Translational Studies Using the MALT1 Inhibitor (Journal of immunotherapy and precision oncology · 2023Article
- Mistuned NF-κB signaling in lymphocytes: lessons from relevant inborn errors of immunity.Clinical and experimental immunology · 2023Article
- The role of the CBM complex in allergic inflammation and disease.The Journal of allergy and clinical immunology · 2022Review
- Combining precision oncology and immunotherapy by targeting the MALT1 protease.Journal for immunotherapy of cancer · 2022Review
- CARD14 Signalling Ensures Cell Survival and Cancer Associated Gene Expression in Prostate Cancer Cells.Biomedicines · 2022Article
- MALT1 positively relates to Th17 cells, inflammation/activity degree, and its decrement along with treatment reflects TNF inhibitor response in ankylosing spondylitis patients.Journal of clinical laboratory analysis · 2022Article
- CARD11 signaling in regulatory T cell development and function.Advances in biological regulation · 2022Review
- MALT1 Is a Targetable Driver of Epithelial-to-Mesenchymal Transition in Claudin-Low, Triple-Negative Breast Cancer.Molecular cancer research : MCR · 2022Article
- The Paracaspase MALT1 in Cancer.Biomedicines · 2022Review
- Pharmacological Inhibition of MALT1 Ameliorates Autoimmune Pathogenesis and Can Be Uncoupled From Effects on Regulatory T-Cells.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic disruption or short-term pharmacological inhibition of MALT1 protease is effective in several preclinical models of autoimmunity and B cell malignancies. Despite these protective effects, the severe reduction in regulatory T cells (Tregs) and the associated IPEX-like pathology occurring upon congenital disruption of the MALT1 protease in mice has raised concerns about the long-term safety of MALT1 inhibition. Here we describe the results of a series of toxicology studies in rat and dog species using MLT-943, a novel potent and selective MALT1 protease inhibitor. While MLT-943 effectively prevented T cell-dependent B cell immune responses and reduced joint inflammation in the collagen-induced arthritis rat pharmacology model, in both preclinical species, pharmacological inhibition of MALT1 was associated with a rapid and dose-dependent reduction in Tregs and resulted in the progressive appearance of immune abnormalities and clinical signs of an IPEX-like pathology. At the 13-week time point, rats displayed severe intestinal inflammation associated with mast cell activation, high serum IgE levels, systemic T cell activation and mononuclear cell infiltration in multiple tissues. Importantly, using thymectomized rats we demonstrated that MALT1 protease inhibition affects peripheral Treg frequency independently of effects on thymic Treg output and development. Our data confirm the therapeutic potential of MALT1 protease inhibitors but highlight the safety risks and challenges to consider before potential application of such inhibitors into the clinic.
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