Abstract
In the present study, Hu-Mikβ1, a humanized mAb directed at the shared IL-2/IL-15Rβ subunit (CD122) was evaluated in patients with T-cell large granular lymphocytic (T-LGL) leukemia. Hu-Mikβ1 blocked the trans presentation of IL-15 to T cells expressing IL-2/IL-15Rβ and the common γ-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-Mikβ1 administration in patients with T-LGL leukemia, but no major clinical responses were observed. One patient who had previously received murine Mikβ1 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-15Rβ (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.
Trial registration:
ClinicalTrials.gov NCT00076180.
Publication types
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Clinical Trial, Phase I
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Research Support, N.I.H., Intramural
MeSH terms
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Aged
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Aged, 80 and over
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Animals
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Antibodies, Monoclonal / administration & dosage*
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal, Humanized / administration & dosage*
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Antibodies, Monoclonal, Humanized / adverse effects
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Antibodies, Monoclonal, Humanized / immunology
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Cell Division / immunology
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Cell Line, Tumor
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Female
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Humans
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Injections, Intravenous
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Interleukin Receptor Common gamma Subunit / immunology
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Interleukin-15 / genetics
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Interleukin-15 / immunology
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Interleukin-2 Receptor beta Subunit / genetics
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Interleukin-2 Receptor beta Subunit / immunology*
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Leukemia, Large Granular Lymphocytic / immunology*
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Leukemia, Large Granular Lymphocytic / therapy*
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Macaca fascicularis
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Male
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Mice
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Middle Aged
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RNA, Messenger / metabolism
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Treatment Outcome
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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IL2RG protein, human
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Interleukin Receptor Common gamma Subunit
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Interleukin-15
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Interleukin-2 Receptor beta Subunit
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RNA, Messenger
Associated data
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ClinicalTrials.gov/NCT00076180