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T and NK cells of B cell NHL patients exert cytotoxicity against lymphoma cells following binding of bispecific tetravalent antibody CD19 × CD3 or CD19 × CD16

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Abstract

Bispecific tetravalent antibodies (TandAb) directed against the B cell surface marker CD19 and activating receptors on T or NK cells (CD19 × CD3 or CD19 × CD16) have shown promising effects in vitro and in preclinical studies. Here, we examine the cytotoxic efficacy of T and NK cells from patients with B cell Non-Hodgkin′s Lymphoma (NHL) against B-lymphoma cells following the binding of the matching TandAb. The addition of CD19 × CD16 TandAb led to a threefold increase in NK cell activation in the presence of B-lymphoma cells. Similarly, T cells displayed a sevenfold increase in cytotoxic activity after the addition of CD19 × CD3 TandAb. Comparison of T and NK cell effector function of patients and healthy controls showed comparable levels of cytotoxic activity in response to lymphoma cells and no reduction in functional activity due to age, disease stage or the type and amount of previous therapy. Thus, T and NK cells of patients with B cell NHL are fully capable of being activated by therapeutic crosslinking antibodies. These results provide a rationale for the use of TandAbs for patients with B cell NHL, particularly in cases where remission with minimal residual disease could be achieved by cytotoxic chemotherapy.

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Acknowledgments

We thank Ms. J. Götzi for her help in collecting the patients′ blood samples. We also thank Dr. E.J. Dettman for critical comments on the manuscript. The CD19 × CD16 TandAb and CD19 × CD3 TandAb were kindly provided by Affimed.

Conflict of interest

Reusch: Affimed: Employment, Patents and Royalties. Little: Affimed: Employment, Equity Ownership, Patents and Royalties. All other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany

    Lisa M. Pörtner, Daniela Brünnert, Frank Neumann, Lars Galonska & Rainer Haas

  2. Institute for Transplantation Diagnostics and Cellular Therapeutics, Heinrich-Heine-University, Moorenstr. 5, 40255, Düsseldorf, Germany

    Kathrin Schönberg, Maryam Hejazi & Markus Uhrberg

  3. Affimed Therapeutics AG, Heidelberg, Germany

    Uwe Reusch & Melvyn Little

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  1. Lisa M. Pörtner
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  2. Kathrin Schönberg
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  3. Maryam Hejazi
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  7. Uwe Reusch
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Correspondence to Markus Uhrberg.

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Pörtner, L.M., Schönberg, K., Hejazi, M. et al. T and NK cells of B cell NHL patients exert cytotoxicity against lymphoma cells following binding of bispecific tetravalent antibody CD19 × CD3 or CD19 × CD16. Cancer Immunol Immunother 61, 1869–1875 (2012). https://doi.org/10.1007/s00262-012-1339-9

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  • DOI: https://doi.org/10.1007/s00262-012-1339-9

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