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CD8 T cell activation after intravenous administration of CD3×CD19 bispecific antibody in patients with non-Hodgkin lymphoma

  • Original Article
  • Bispecific Antibody, Cytokines, Phase I Study, Non-Hodgkin Lymphoma, T Cell Activation
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

A bispecific antibody directed to T and B cells (CD3×CD19 bsAb) was daily infused intravenously in escalating doses from 10 μg up to 5 mg in three patients with chemotherapy-resistant non-Hodgkin lymphoma; in this way we aimed to activate T cells to kill the malignant B cells. Only limited toxicity was observed, consisting of moderate fever preceded by chills or shivers and mild thrombocytopenia. No human anti-(mouse Ig) antibodies were found. Pharmacokinetics showed at 1/2 of 10.5 h with peak levels of 200–300 ng/ml after infusion of 2.5 mg bsAb. bsAb in serum was functionally active in vitro. After bsAb infusion a rise in serum tumour necrosis factor α was observed, accompanied by an increase in soluble CD8 and to some extent in soluble interleukin-2 receptor (IL-2R), but not in interferon γ, IL-4 or soluble CD4. No evidence was found for monocyte activation (no increases in IL-6, IL-8 or IL-1ß in serum). No gross changess in histology or number of IL-2R+, CD4+ or CD8+ cells were found in the lymph nodes after therapy, but one patient showed activated CD8+ T cells within the tumour nodules. In conclusion, after intravenously administered CD3×CD19 bsAb only moderate toxicity was found, probably due to CD8+ T cell activation and cytokine release, without CD4+ T cell activation.

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Author notes

  1. Gijsbert C. de Gast

    Present address: Department of Haematology, University Hospital Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands

Authors and Affiliations

  1. Department of Immunology, University Hospital Utrecht, The Netherlands

    Gijsbert C. de Gast, Inez-Anne Haagen, Ashley J. Duits, Anette J. G. van Dijk, Wim B. M. de Lau & Bert J. E. G. Bast

  2. Department of Haematology, University Hospital Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands

    Anja A. van Houten

  3. Department of Pathology, University Hospital Utrecht, The Netherlands

    Sigrid C. Klein, Roel A. de Weger & Thea M. Vroom

  4. Department of Pathology, University of Cambridge, UK

    Mike R. Clark & Jenny Phillips

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  1. Gijsbert C. de Gast
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de Gast, G.C., Haagen, IA., van Houten, A.A. et al. CD8 T cell activation after intravenous administration of CD3×CD19 bispecific antibody in patients with non-Hodgkin lymphoma. Cancer Immunol Immunother 40, 390–396 (1995). https://doi.org/10.1007/BF01525390

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  • DOI: https://doi.org/10.1007/BF01525390

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