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4185 Blocking the CD47-Sirpa Axis Enhances Tafasitamab-Mediated Phagocytosis

Program: Oral and Poster Abstracts
Session: 622. Lymphomas: Translational–Non-Genetic: Poster III
Hematology Disease Topics & Pathways:
Research, Biological therapies, Antibody Therapy, Combination therapy, Therapies
Monday, December 12, 2022, 6:00 PM-8:00 PM

Alexander Biedermann1*, Doris Mangelberger-Eberl2*, Dimitrios Mougiakakos, MD3, Maike Büttner-Herold4*, Cindy Flamann5*, Christian Kellner6*, Sarah Altmeyer7*, Jörg Bittenbring8*, Christian Augsberger2*, Maria Patra-Kneuer, Ph.D.2*, Karin Landgraf2*, Kristina Ilieva-Babinski2*, Stefan Haskamp1*, Fabian Beier, MD9*, Simon Voelkl, PhD10*, Christian Pallasch11*, Benedikt Jacobs, MD12*, Stefan Steidl, Ph.D.2*, Christina Heitmüller, Ph.D.2*, Andreas Mackensen, MD13* and Heiko Bruns, PhD14*

1University Hospital Erlangen, Erlangen, Germany
2MorphoSys AG, Planegg, Germany
3Otto von Guericke University Magdeburg, Magdeburg, Germany
4Department of Nephropathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
5Dept. of Internal Medicine 5 – Hematology/Oncology, University of Erlangen, Erlangen, Germany
6Department of Transfusion Medicine, Cell Therapeutics and Hemostaseology, University Hospital, LMU Munich, Munich, Germany
7Saarland University Hospital, Homburg, DEU
8Department of Hematology, Oncology, Clinical Immunology, Rheumatology, Medical School, University of Saarland, Homburg, Germany
9Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, NRW, Germany
10Department of Internal Medicine 5 - Hematology/Oncology, University Hospital of Erlangen, Erlangen, Germany
11University Hospital of Cologne, Cologne, Germany
12Department of Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany
13Dept. of Internal Medicine 5 - Hematology/Oncology, University Hospital of Erlangen, Erlangen, Germany
14Dept. of Internal Medicine 5 - Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany


Around 40% of diffuse large B cell lymphoma (DLBCL) patients have refractory disease or experience relapse, thus highlighting the need for novel, more effective therapies (Coiffier et al). The immunotherapy Tafasitamab (MOR208) is an Fc-modified, humanized, monoclonal anti-CD19 antibody approved in combination with lenalidomide as a second line of therapy for R/R DLBCL. Tafasitamab mediates its therapeutic effect directly or via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Macrophages represent a key component of the DLBCL microenvironment and are critical effectors of antibody therapies (Uchida et al). However, ADCP is reportedly counteracted by increased expression of the immune checkpoint molecule CD47 on lymphoma targets (Chao et al). In addition, the inhibitory receptor of CD47, signal regulatory protein alpha (SIRPα) is increased on macrophages from patients with follicular lymphoma who relapse or progress after frontline lenalidomide and rituximab (Marques-Piubelli et al).

Aim of the study

The current study investigates the impact of the CD47-SIRPα axis on tafasitamab-mediated phagocytosis and the potential of concomitant treatment with an anti-CD47 blocking antibody to improve its efficacy.


We show that both, CD47 and its inhibitory receptor SIRPa were elevated in lymph node biopsies from DLBCL patients. CD47 expression was evaluated in 6 DLBCL patients and 5 healthy controls and SIRPα was evaluated in 9 patients and 7 controls. In fact, increased expression of SIRPa on macrophages correlated with decreased ADCP activity of tafasitamab, and CRISPR-mediated CD47 overexpression on lymphoma targets impaired tafasitamab-mediated phagocytosis, in vitro. Combination of tafasitamab and an anti-CD47 blocking antibody enhanced ADCP activity of in vitro generated macrophages. Furthermore, lymphoma cells with low CD19 expression were efficiently eliminated by the combination therapy. Importantly, the combination enhanced tafasitamab-mediated phagocytosis of primary DLBCL cells using primary, patient-derived lymphoma-associated macrophages (LAMs) as effectors, in an autologous setting.


Our results show increased expression of CD47-SIRPa axis in primary DLBCL samples and indicate that CD47 blockade can enhance the phagocytic potential of tumor-targeting immunotherapies such as tafasitamab. Our findings suggest that there is merit in exploring the clinical utility of combining tafasitamab with an anti-CD47 blocking antibody in lymphoma.

Disclosures: Mangelberger-Eberl: Morphosys: Current Employment, Current equity holder in publicly-traded company. Mougiakakos: Jazz Pharma: Honoraria; Gilead: Honoraria; Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Augsberger: Morphosys: Current Employment. Patra-Kneuer: Morphosys: Current Employment, Patents & Royalties. Landgraf: Morphosys: Current Employment, Current equity holder in publicly-traded company. Ilieva-Babinski: Morphosys: Current Employment. Beier: Alexion: Honoraria; Sobi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria; Pfizer: Honoraria. Steidl: Morphosys: Current Employment. Heitmüller: Morphosys: Current Employment. Mackensen: Kite/Gilead: Honoraria; Miltenyi Biomedicine: Honoraria; BMS/Celgene: Honoraria; Novartis: Honoraria.

*signifies non-member of ASH