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• W3048853054 abstract "// Yaya Chu 1 , * , Aradhana Awasthi 1 , * , Sanghoon Lee 1 , 2 , Dina Edani 1 , Changhong Yin 1 , Jessica Hochberg 1 , Tishi Shah 1 , Tae-Hoon Chung 6 , Janet Ayello 1 , Carmella van de Ven 1 , Christian Klein 7 , Dean Lee 8 and Mitchell S. Cairo 1 , 2 , 3 , 4 , 5 1 Department of Pediatrics, New York Medical College, Valhalla, NY, USA 2 Department of Cell Biology &#x0026; Anatomy, New York Medical College, Valhalla, NY, USA 3 Department of Microbiology &#x0026; Immunology, New York Medical College, Valhalla, NY, USA 4 Department of Medicine, New York Medical College, Valhalla, NY, USA 5 Department of Pathology, New York Medical College, Valhalla, NY, USA 6 Cancer Science Institute of Singapore, National University of Singapore, Singapore 7 Roche Pharmaceutical Research &#x0026; Early Development, Roche Innovation Center, Zurich, Switzerland 8 Department of Pediatrics, Nationwide Children&#x2019;s Hospital, Columbus, Ohio, USA * Co-first authors Correspondence to: Mitchell S. Cairo, email: mitchell_cairo@nymc.edu Keywords: Obinutuzumab; rituximab; survival; primary mediastinal large B-cell lymphoma; antibody-dependent cellular cytotoxicity Received: March 06, 2020     Accepted: July 14, 2020     Published: August 11, 2020 ABSTRACT Primary mediastinal large B-cell lymphoma (PMBL), a distinct mature B-cell lymphoma, expresses CD20 and has recently been successfully treated with the combination of a type I anti-CD20 monoclonal antibody, rituximab, with multiple combination chemotherapy regimens. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody (mAb), recognizing a unique CD20 extracellular membrane epitope with enhanced antibody dependent cellular cytotoxicity (ADCC) vs rituximab. We hypothesize that obinutuzumab vs rituximab will significantly enhance in-vitro and in-vivo cytotoxicity against PMBL. PMBL cells were treated with equal dose of obinutuzumab and rituximab for 24 hours (1&#x2013;100 &#x03BC;g/ml). ADCC were performed with ex-vivo expanded natural killer cells at 10:1 E: T ratio. Mice were xenografted with intravenous injections of luciferase expressing Karpas1106P cells and treated every 7 days for 8 weeks. Tumor burden was monitored by IVIS spectrum system. Compared with rituximab, obinutuzumab significantly inhibited PMBL cell proliferation ( p = 0.01), promoted apoptosis ( p = 0.05) and enhanced ADCC ( p = 0.0002) against PMBL. Similarly, in PMBL xenografted NOD scid gamma mice, obinutuzumab significantly enhanced survival than rituximab when treated with equal doses ( p = 0.05). Taken together our results suggest that obinutuzumab significantly enhanced natural killer cytotoxicity, reduced PMBL proliferation and prolonged the overall survival in humanized PMBL xenografted NOD scid gamma mice." @default.
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• W3048853054 date "2020-08-11" @default.
• W3048853054 modified "2023-10-01" @default.
• W3048853054 title "Obinutuzumab (GA101) vs. rituximab significantly enhances cell death, antibody-dependent cytotoxicity and improves overall survival against CD20+ primary mediastinal B-cell lymphoma (PMBL) in a xenograft NOD-scid IL2Rgnull (NSG) mouse model: a potential targeted agent in the treatment of PMBL" @default.
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• W3048853054 doi "https://doi.org/10.18632/oncotarget.27691" @default.
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