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Obinutuzumab ( GA 101) compared to rituximab significantly enhances cell death and antibody‐dependent cytotoxicity and improves overall survival against CD 20 + rituximab‐sensitive/‐resistant Burkitt lymphoma ( BL ) and precursor B‐acute lymphoblastic leukaemia (pre‐B‐ ALL ): potential targeted therapy in patients with poor risk CD 20 + BL and pre‐B‐ ALL
Author(s) -
Awasthi Aradhana,
Ayello Janet,
Van de Ven Carmella,
Elmacken Mona,
Sabulski Anthony,
Barth Matthew J.,
Czuczman Myron S.,
Islam Humayun,
Klein Christian,
Cairo Mitchell S.
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13764
Subject(s) - obinutuzumab , antibody dependent cell mediated cytotoxicity , rituximab , cd20 , raji cell , medicine , lymphoma , monoclonal antibody , immunology , antibody , cancer research
Summary Obinutuzumab is a novel glycoengineered Type‐ II CD 20 monoclonal antibody. CD 20 is expressed in approximately 100% of children and adolescents with Burkitt lymphoma ( BL ) and 40% with precursor B‐cell acute lymphoblastic leukaemia (pre‐B‐ ALL ). We evaluated the anti‐tumour activity of obinutuzumab versus rituximab against rituximab‐resistant (Raji 4 RH ) and ‐sensitive (Raji) BL and pre‐B‐ ALL (U698‐M) cells in vitro and in human BL or Pre‐B‐ ALL xenografted mice. We demonstrated that obinutuzumab compared to rituximab significantly enhanced cell death against Raji 35·6 ± 3·1% vs. 25·1 ± 2·0%, ( P = 0·001), Raji4 RH 19·7 ± 2·2% vs. 7·9 ± 1·5% ( P = 0·001) and U‐698‐M 47·3 ± 4·9% vs. 23·2 ± 0·5% ( P = 0·001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody‐dependent cellular cytotoxicity ( ADCC ) with K562‐ IL 15‐41 BBL expanded NK cells against Raji 73·8 ± 8·1% vs. 56·81 ± 4·6% ( P = 0·001), Raji‐4 RH 40·0 ± 1·6% vs. 0·5 ± 1·1% ( P = 0·001) and U‐698‐M 70·0 ± 1·6% vs. 45·5 ± 0·1% ( P = 0·001), respectively. Overall survival in tumour xenografted mice receiving 30 mg/kg of obinutuzumab was significantly increased when compared to those receiving 30 mg/kg of rituximab in BL ; Raji ( P = 0·05), Raji4 RH ( P = 0·02) and U698‐M ( P = 0·03), respectively. These preclinical data suggest obinutuzumab is significantly superior to rituximab in inducing cell death, ADCC and against rituximab‐sensitive/‐resistant BL and pre‐B‐ ALL xenografted mice. Taken together, these preclinical results provide evidence to suggest that future investigation of obinutuzumab is warranted in patients with relapsed/refractory CD 20 + BL and/or pre‐B‐ ALL .