• Je něco špatně v tomto záznamu ?

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

M. Patra-Kneuer, G. Chang, W. Xu, C. Augsberger, M. Grau, M. Zapukhlyak, K. Ilieva, K. Landgraf, D. Mangelberger-Eberl, K. Yousefi, P. Berning, KS. Kurz, G. Ott, P. Klener, C. Khandanpour, P. Horna, J. Schanzer, S. Steidl, J. Endell, C....

. 2023 ; 14 (-) : 1220558. [pub] 20230731

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc23016798

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23016798
003      
CZ-PrNML
005      
20231026105532.0
007      
ta
008      
231013s2023 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3389/fimmu.2023.1220558 $2 doi
035    __
$a (PubMed)37600821
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Patra-Kneuer, Maria $u Translational Research, MorphoSys AG, Planegg, Germany
245    10
$a Activity of tafasitamab in combination with rituximab in subtypes of aggressive lymphoma / $c M. Patra-Kneuer, G. Chang, W. Xu, C. Augsberger, M. Grau, M. Zapukhlyak, K. Ilieva, K. Landgraf, D. Mangelberger-Eberl, K. Yousefi, P. Berning, KS. Kurz, G. Ott, P. Klener, C. Khandanpour, P. Horna, J. Schanzer, S. Steidl, J. Endell, C. Heitmüller, G. Lenz
520    9_
$a 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.
650    _2
$a myši $7 D051379
650    _2
$a zvířata $7 D000818
650    _2
$a myši inbrední NOD $7 D016688
650    _2
$a myši SCID $7 D016513
650    _2
$a rituximab $x farmakologie $x terapeutické užití $7 D000069283
650    _2
$a leukocyty mononukleární $7 D007963
650    _2
$a humanizované monoklonální protilátky $7 D061067
650    12
$a Burkittův lymfom $x farmakoterapie $7 D002051
650    12
$a difúzní velkobuněčný B-lymfom $x farmakoterapie $7 D016403
655    _2
$a časopisecké články $7 D016428
700    1_
$a Chang, Gaomei $u Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany
700    1_
$a Xu, Wendan $u Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany
700    1_
$a Augsberger, Christian $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Grau, Michael $u Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany
700    1_
$a Zapukhlyak, Myroslav $u Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany
700    1_
$a Ilieva, Kristina $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Landgraf, Karin $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Mangelberger-Eberl, Doris $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Yousefi, Kasra $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Berning, Philipp $u Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany
700    1_
$a Kurz, Katrin S $u Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany
700    1_
$a Ott, German $u Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany
700    1_
$a Klener, Pavel $u Institute of Pathological Physiology, First Faculty of Medicine, Charles University Prague, Prague, Czechia $u First Medical Department, Department of Hematology, Charles University General Hospital Prague, Prague, Czechia
700    1_
$a Khandanpour, Cyrus $u Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany $u Hematology and Oncology Clinic, University of Lübeck and University Hospital Schleswig-Holstein, Lübeck, Germany
700    1_
$a Horna, Pedro $u Division of Hematopathology, Mayo Clinic, Rochester, MN, United States
700    1_
$a Schanzer, Jürgen $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Steidl, Stefan $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Endell, Jan $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Heitmüller, Christina $u Translational Research, MorphoSys AG, Planegg, Germany
700    1_
$a Lenz, Georg $u Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany
773    0_
$w MED00181405 $t Frontiers in immunology $x 1664-3224 $g Roč. 14, č. - (2023), s. 1220558
856    41
$u https://pubmed.ncbi.nlm.nih.gov/37600821 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20231013 $b ABA008
991    __
$a 20231026105527 $b ABA008
999    __
$a ok $b bmc $g 2000378 $s 1203160
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 14 $c - $d 1220558 $e 20230731 $i 1664-3224 $m Frontiers in immunology $n Front Immunol $x MED00181405
LZP    __
$a Pubmed-20231013

Najít záznam

Citační ukazatele

Možnosti archivace