NYMC Faculty Publications

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

DOI

10.18632/oncotarget.27691

Journal Title

Oncotarget

First Page

3035

Last Page

3047

Document Type

Article

Publication Date

8-11-2020

Department

Pediatrics

Second Department

Medicine

Third Department

Pathology, Microbiology and Immunology

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 (1-100 μg/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.

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