Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma

Frontiers in Immunology

Immunology

German Ott¹  Katrin S. Kurz¹  Myroslav Zapukhlyak²  Philipp Berning²  Wendan Xu²  Gaomei Chang²  Michael Grau²  Georg Lenz²  Cyrus Khandanpour³  Pedro Horna⁴  Pavel Klener⁵  Christina Heitmüller⁶  Kristina Ilieva⁶  Karin Landgraf⁶  Jürgen Schanzer⁶  Doris Mangelberger-Eberl⁶  Jan Endell⁶  Maria Patra-Kneuer⁶  Stefan Steidl⁶  Kasra Yousefi⁶  Christian Augsberger⁶ 

[1] Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany;Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany;Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany;Hematology and Oncology Clinic, University of Lübeck and University Hospital Schleswig-Holstein, Lübeck, Germany;Division of Hematopathology, Mayo Clinic, Rochester, MN, United States;Institute of Pathological Physiology, First Faculty of Medicine, Charles University Prague, Prague, Czechia;First Medical Department, Department of Hematology, Charles University General Hospital Prague, Prague, Czechia;Translational Research, MorphoSys AG, Planegg, Germany;

关键词: antibody therapy;    lymphoma;    tumor immunology;    CD19;    CD20;    tafasitamab;    rituximab;   

DOI  :  10.3389/fimmu.2023.1220558

 received in 2023-05-10, accepted in 2023-07-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundDespite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects.MethodsAntibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL).ResultsThree different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model.ConclusionThis study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma in vitro and in vivo.

【 授权许可】

Unknown   
Copyright © 2023 Patra-Kneuer, Chang, Xu, Augsberger, Grau, Zapukhlyak, Ilieva, Landgraf, Mangelberger-Eberl, Yousefi, Berning, Kurz, Ott, Klener, Khandanpour, Horna, Schanzer, Steidl, Endell, Heitmüller and Lenz