Preclinical and phase I clinical trial of blockade of IL-15 using Mikbeta1 monoclonal antibody in T cell large granular lymphocyte leukemia.

ABSTRACT: Twelve patients with T cell large granular lymphocyte leukemia and associated hematocytopenia were treated in a phase I dose-escalation trial with the murine monoclonal antibody Mikbeta1. Mikbeta1 identifies CD122, the beta-subunit shared by the IL-2 and IL-15 receptors. At the doses administered in this study the antibody inhibited the actions of IL-15 on both natural killer and T cells and that of IL-2 when the intermediate-affinity IL-2 receptor was expressed. Mikbeta1 treatment was not associated with significant toxicity or with the development of an immune response to the infused monoclonal antibody. At these doses of Mikbeta1, >95% saturation of the IL-2/IL-15beta receptor (CD122) on the surfaces of the leukemic cells was achieved. Furthermore, in seven patients this led to the down

SUBMITTER: Morris JC 

PROVIDER: S-EPMC1326174 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature