First-in-class Cancer Immunotherapy Drug in Clinical Trial
A small molecule has entered a novel clinical trial for cancer immunotherapy. The molecule inhibits an enzyme called MALT1 that plays a critical role in suppressing immune reactions against tumor cells. Preclinical studies showed that blocking MALT1 activity results in immune reactivation and boosts an anti-tumor immune response. Originally developed under the lead of Helmholtz Zentrum München, the research center has licensed the first-in-class MALT1 inhibitor to the US biotech company Monopteros Therapeutics who is now running the clinical trial.
Cancer immunotherapy aims to improve the ability of the patient’s immune system to fight and eliminate the tumor cells. The immune cell environment surrounding tumors is highly relevant for the effectiveness of immune-oncology approaches. Especially the presence of regulatory T cells (Tregs) is often responsible for immunosuppression, which prevents the destruction of tumor cells. The suppressive function of Tregs relies on the activity of the enzyme MALT1. Without MALT1 activity, Tregs are not able to block the immune response, which makes the enzyme a promising target to boost cancer immunotherapy.
Daniel Krappmann*, molecular immunologist at Helmholtz Zentrum München, discovered and developed with his team the first small molecules that have the ability to inhibit MALT1. Studies in Munich and Boston demonstrated that inhibiting MALT1 with those molecules reprograms regulatory T cells and reactivates an immune response in skin cancer models in mice. To foster rapid preclinical and clinical development, Helmholtz Zentrum München has licensed MALT1 inhibitors to Monopteros Therapeutics. “We are thrilled to see that Monopteros launched a clinical trial with the first-in-class MALT1 inhibitor”, says Daniel Krappmann. “This drug holds great potential for improving anti-tumor immunity and, if successful, we hope that more patients will benefit from cancer immunotherapy”.
Matthias Tschöp, CEO of Helmholtz Zentrum München: “Transferring breakthrough findings from basic research to benefit patients is one of our highest priorities. The journey of this small molecule, originally developed at Helmholtz Zentrum München and now in clinical trials, marks a milestone in our translational endeavors.”
Monopteros runs the clinical trial with the inhibitor MPT-0118 at its US based study centers. The trial aims to evaluate the safety and efficacy of MPT-0118. Patients receive it orally in form of a tablet. Further information on the clinical trial is available at monopterostx.com.
Innovation and translation at Helmholtz Zentrum München
To pursue its vision of a healthier society, Helmholtz Zentrum München aims to accelerate the development of novel assets for prevention, personalized therapeutics, diagnostics as well as medical devices. Special emphasis is placed on drug discovery and development as an activity across all research fields covering new small molecules, biologics, vaccines as well as immune, gene and cell therapies. For more information, please visit: <link en/innovation-translation/ - extern>https://backup.helmholtz-munich.de/en/innovation-translation/ </link>
*Daniel Krappmann leads the research unit for cellular signal integration at Helmholtz Zentrum München. He is an associated professor for biology at LMU Munich.
Nagel et al., 2012: <link www.cell.com/cancer-cell/fulltext/S1535-6108(12)00482-5 - extern>Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL.</link> Cancer Cell, DOI: 10.1016/j.ccr.2012.11.002
Rosenbaum et al., 2019: <link www.nature.com/articles/s41467-019-10203-2 - extern>Bcl10-controlled Malt1 paracaspase activity is key for the immune suppressive function of regulatory T cells</link>. Nature communications, DOI: 10.1038/s41467-019-10203-2
Di Pilato et al., 2019: <link www.nature.com/articles/s41586-019-1215-2 - extern>Targeting the CBM complex causes T reg cells to prime tumours for immune checkpoint therapy.</link> Nature, DOI: 10.1038/s41586-019-1215-2