TY - JOUR
T1 - Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma
AU - Patra-Kneuer, Maria
AU - Chang, Gaomei
AU - Xu, Wendan
AU - Augsberger, Christian
AU - Grau, Michael
AU - Zapukhlyak, Myroslav
AU - Ilieva, Kristina
AU - Landgraf, Karin
AU - Mangelberger-Eberl, Doris
AU - Yousefi, Kasra
AU - Berning, Philipp
AU - Kurz, Katrin S.
AU - Ott, German
AU - Klener, Pavel
AU - Khandanpour, Cyrus
AU - Horna, Pedro
AU - Schanzer, Jürgen
AU - Steidl, Stefan
AU - Endell, Jan
AU - Heitmüller, Christina
AU - Lenz, Georg
N1 - Publisher Copyright:
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.
PY - 2023
Y1 - 2023
N2 - Background: Despite 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. Methods: Antibody 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). Results: Three 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. Conclusion: This 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.
AB - Background: Despite 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. Methods: Antibody 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). Results: Three 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. Conclusion: This 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.
UR - http://www.scopus.com/inward/record.url?scp=85168111492&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2023.1220558
DO - 10.3389/fimmu.2023.1220558
M3 - Journal articles
C2 - 37600821
AN - SCOPUS:85168111492
SN - 1664-3224
VL - 14
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1220558
ER -