The Fc-engineered CD19 antibody MOR208 (XmAb5574) induces natural killer cell-mediated lysis of acute lymphoblastic leukemia cells from pediatric and adult patients

C Kellner,E A Zhukovsky,A Pötzke,M Peipp,M Brüggemann,M Kneba,R Repp,A Schrauder,A Humpe,M Schrappe,M Gramatzki

doi:10.1038/leu.2012.373

C Kellner, E A Zhukovsky + Show 9 more

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https://doi.org/10.1038/leu.2012.373

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Abstract

The Fc-engineered CD19 antibody MOR208 (XmAb5574) induces natural killer cell-mediated lysis of acute lymphoblastic leukemia cells from pediatric and adult patients

Highlights

The introduction of therapeutic antibodies such as the CD20 antibody rituximab has improved the treatment options of patients with B-cell lymphomas
B-lineage acute lymphoblastic leukemia (ALL) patients often do not benefit from this therapeutic option, because CD20 is not expressed in the majority of cases, especially when the disease originated from more immature B-precursor cells
To study the clinically relevant, Fc-mediated effector functions, we investigated the contributions of various effector cells, as well as complement, to the cytotoxic profile of MOR208 using standard 51Cr release experiments (Figure 1a; further technical information is provided in the Supplementary Materials and methods section)

Summary

Introduction

The introduction of therapeutic antibodies such as the CD20 antibody rituximab has improved the treatment options of patients with B-cell lymphomas. Results from animal models and clinical trials suggested that Fcg-receptor-mediated effector mechanisms are essential for the activity of individual therapeutic antibodies.[9,10] In patients treated with rituximab, in particular, the homozygous expression of the FcgRIIIa-158V/V allotype, which has higher binding affinity for Immunoglobulin G (IgG) than the FcgRIIIa-158F/F variant, was correlated with improved response rates and overall survival.[11] These observations suggest a substantial contribution of FcgRIIIapositive effector cells, such as natural killer (NK) cells and macrophages, in antibody therapy. Positive tumor cell lines and primary tumor cells from patients with different B-cell malignancies including chronic lymphocytic leukemia or adult ALL.[7,14,15] These results motivated us to characterize the activity of MOR208 against ALL in more detail using primary ALL cells isolated from both adult and pediatric patients (Supplementary Table 1).

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Conclusion