SummaryObinutuzumab is a novel glycoengineered Type-II CD20 monoclonal antibody. CD20 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 4RH) 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 35Á6 AE 3Á1% vs. 25Á1 AE 2Á0%, (P = 0Á001), Raji4RH 19Á7 AE 2Á2% vs. 7Á9 AE 1Á5% (P = 0Á001) and U-698-M 47Á3 AE 4Á9% vs. 23Á2 AE 0Á5% (P = 0Á001), respectively. Obinutuzumab versus rituximab also induced a significant increase in antibody-dependent cellular cytotoxicity (ADCC) with K562-IL15-41BBL expanded NK cells against Raji 73Á8 AE 8Á1% vs. 56Á81 AE 4Á6% (P = 0Á001), Raji-4RH 40Á0 AE 1Á6% vs. 0Á5 AE 1Á1% (P = 0Á001) and U-698-M 70Á0 AE 1Á6% vs. 45Á5 AE 0Á1% (P = 0Á001), 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 = 0Á05), Raji4RH (P = 0Á02) and U698-M (P = 0Á03), 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 CD20 + BL and/or pre-B-ALL.

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