On April 8, 2019 4SC AG (4SC, FSE Prime Standard: VSC) reported preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 that confirm domatinostat’s mode of action in Merkel cell carcinoma (MCC) (Press release, 4SC, APR 8, 2019, View Source [SID1234535040]). The data were presented by Prof. Dr. Dr. Jürgen C. Becker, Department of Translational Skin Cancer Research at the University Hospital Essen, Germany, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. The AACR (Free AACR Whitepaper) Meeting took place at the Georgia World Congress Center in Atlanta, USA, from 29 March to 3 April 2019.

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Merkel cell carcinoma – tumor cells hide from the immune system

MCC is a rare, highly aggressive skin cancer often caused by either infection with Merkel cell polyomavirus or extensive UV exposure. Patients suffer from rapidly enlarging nodules that are between 0.5 and 5 cm in diameter, while the tumor aggressively spreads through the blood vessels to lymph nodes and many organs.

Although immune checkpoint inhibitors have shown compelling clinical activity in MCC, in some patients the tumor cells are very adept at evading the immune system. The tumor cells and its microenvironment prevent immune cells from entering the tumor and limit the presentation of tumor-signals on their surface. For these patients, refractory to or relapsing on checkpoint inhibitor therapy, currently no further treatment options are available.

Prof. Dr. Dr. Jürgen C. Becker explained: "In previous experiments we demonstrated that the immune escape mechanisms of MCC cells were epigenetically reversible1. Therefore, we were highly interested in testing the effect of 4SC’s domatinostat, an orally available, epigenetically active small molecule inhibitor targeting histone deacetylases class I, on MCC cell lines.

"Our new data demonstrate that domatinostat increased the presentation of tumor signals on the cells’ surface, stopped MCC cells from dividing and even induced cell death. All these effects were specific for MCC cell lines and did not occur in healthy control cells."

Frank Hermann, M.D., Chief Development Officer of 4SC, said: "We thank our collaborators for the dedication and energy devoted to their research with domatinostat. The fact that domatinostat counteracts the immune escape of MCC at different levels suggests that the combination of domatinostat with checkpoint inhibitors is potentially a promising therapeutic strategy in MCC and we plan to initiate a potentially pivotal clinical trial later this year."

Abstract ID 2368: Domatinostat increases apoptosis, G2M cell-cycle arrest and immunogenicity of Merkel cell carcinoma

The poster is available on 4SC’s website.

Reference:

1 Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma. C. Ritter, K. Fan, A. Paschen, S. Reker Hardrup, S. Ferrone, P. Nghiem, S. Ugurel, D. Schrama, and J. C. Becker. Sci Rep. 2017 May 23;7(1):2290. doi: 10.1038/s41598-017-02608-0