Phase 1 trial of IL-15 trans presentation blockade using humanized Mik?1 mAb in patients with T-cell large granular lymphocytic leukemia.

ABSTRACT: In the present study, Hu-Mik?1, a humanized mAb directed at the shared IL-2/IL-15R? subunit (CD122) was evaluated in patients with T-cell large granular lymphocytic (T-LGL) leukemia. Hu-Mik?1 blocked the trans presentation of IL-15 to T cells expressing IL-2/IL-15R? and the common ?-chain (CD132), but did not block IL-15 action in cells that expressed the heterotrimeric IL-15 receptor in cis. There was no significant toxicity associated with Hu-Mik?1 administration in patients with T-LGL leukemia, but no major clinical responses were observed. One patient who had previously received murine Mik?1 developed a measurable Ab response to the infused Ab. Nevertheless, the safety profile of this first in-human study of the humanized mAb to IL-2/IL-15R? (CD122) supports its evaluation in disorders such as refractory celiac disease, in which IL-15 and its receptor have been proposed to play a critical role in the pathogenesis and maintenance of disease activity.

SUBMITTER: Waldmann TA 

PROVIDER: S-EPMC3548167 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature