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Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human α/β T cell receptor

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Summary

A murine IgG2b monoclonal antibody directed to the constant part of the human α/β T cell receptor (BMA031) was investigated in a pilot study as an initial treatment for acute graft-versus-host disease (aGvHD) after allogeneic bone marrow transplantation. The treatment protocol consisted of 5 mg BMA031 on 5 consecutive days with continuation of the prophylactic baseline immuno suppression using cyclosporin. Seven patients with grades II–III acute graft-versus-host disease were entered on the protocol and six patients completed the full treatment course. Mild to moderate acute adverse reactions to the first BMA031 infusion occurred in three patients. A nearly complete decline of circulating T lymphocytes was observed during BMA031 therapy, but the T cells returned to pretreatment values within 1 week after the last infusion. Serum pharmacokinetics of free antibody best fitted to a two-compartment open model with a mean initial half-life of 6 h and an estimated mean terminal half-life of 40 h. One patient developed antimurine antibodies of the IgM subclass. In five patients a complete and sustained resolution of all disease manifestations was attained, while in one patient a temporary response of skin involvement with aGvHD was noted. These results indicate that BMA031 can be safely administered as initial treatment of aGvHD. The therapeutic responses observed warrant its further clinical evaluation in this setting.

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Correspondence to Dietrich W. Beelen.

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Beelen, D.W., Grosse-Wilde, H., Ryschka, U. et al. Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human α/β T cell receptor. Cancer Immunol Immunother 34, 97–102 (1991). https://doi.org/10.1007/BF01741342

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Key words

  • Bone marrow transplantation
  • Acute graft-versus-host disease
  • Monoclonal antibody