HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies

Author:

Bobrowicz Malgorzata12,Dwojak Michal12,Pyrzynska Beata1,Stachura Joanna12,Muchowicz Angelika1,Berthel Elise3,Dalla-Venezia Nicole3,Kozikowski Mieszko14,Siernicka Marta12,Miazek Nina1,Zapala Piotr1,Domagala Antoni1,Bojarczuk Kamil1,Malenda Agata5,Barankiewicz Joanna56,Graczyk-Jarzynka Agnieszka1,Zagozdzon Agnieszka1,Gabrysiak Magdalena1,Diaz Jean-Jacques3,Karp Marta7,Lech-Maranda Ewa56,Firczuk Malgorzata1,Giannopoulos Krzysztof78,Efremov Dimitar G.9ORCID,Laurenti Luca10,Baatout Dunja1112,Frenzel Lukas1112,Malinowska Agata13,Slabicki Mikolaj14,Zenz Thorsten1415,Zerrouqi Abdessamad1,Golab Jakub116,Winiarska Magdalena1

Affiliation:

1. Department of Immunology and

2. Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland;

3. Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS, UMR5286, Lyon, France;

4. Department of Urology, Centre of Postgraduate Medical Education, European Health Centre, Otwock, Poland;

5. Institute of Hematology and Transfusion Medicine, Warsaw, Poland;

6. Department of Hematology and Transfusion Medicine, Centre of Postgraduate Medical Education, Warsaw, Poland;

7. Department of Hematology, St John's Cancer Center in Lublin, Poland;

8. Department of Experimental Hematology, Medical University of Lublin, Lublin, Poland;

9. Molecular Hematology, International Centre for Genetic Engineering & Biotechnology, Trieste, Italy;

10. Department of Hematology, Catholic University Hospital “A. Gemelli,” Rome, Italy;

11. Department I Internal Medicine, University Hospital Cologne, Cologne, Germany;

12. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany;

13. Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland;

14. Molecular Therapy in Hematology and Oncology & Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany;

15. Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany; and

16. Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland

Abstract

Key Points HDAC6 inhibition represents a novel strategy to improve the efficacy of anti-CD20 mAbs. HDAC6 inhibition increases CD20 levels by enhancing CD20 protein synthesis without affecting the gene expression.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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