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

Thomas A. Waldmann, Kevin C. Conlon, Donn M. Stewart, Tat Yana A. Worthy, John Edward Janik, Thomas A. Fleisher, Paul S. Albert, William D. Figg, Shawn D. Spencer, Mark Raffeld, Jean R. Decker, Carolyn K. Goldman, Bonita R. Bryant, Michael N. Petrus, Stephen P. Creekmore, John C. Morris

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

In the present study, Hu-Mikβ 1, 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-Mikβ 1 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-Mikβ 1 administration in patients with T-LGL leukemia, but no major clinical responses were observed. One patient who had previously received murine Mikβ 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-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. The protocol is registered with www.clinicaltrials.gov as number NCT 00076180.

Original languageEnglish (US)
Pages (from-to)476-484
Number of pages9
JournalBlood
Volume121
Issue number3
DOIs
StatePublished - Jul 17 2013

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Large Granular Lymphocytic Leukemia
Interleukin-15
T-cells
Interleukin-15 Receptors
Interleukin-2
Celiac Disease
Refractory materials
Toxicity
Maintenance
T-Lymphocytes
Safety

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Waldmann, T. A., Conlon, K. C., Stewart, D. M., Worthy, T. Y. A., Janik, J. E., Fleisher, T. A., ... Morris, J. C. (2013). Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-Beta-1 mAb in patients with T-cell large granular lymphocytic leukemia. Blood, 121(3), 476-484. https://doi.org/10.1182/blood-2012-08-450585

Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-Beta-1 mAb in patients with T-cell large granular lymphocytic leukemia. / Waldmann, Thomas A.; Conlon, Kevin C.; Stewart, Donn M.; Worthy, Tat Yana A.; Janik, John Edward; Fleisher, Thomas A.; Albert, Paul S.; Figg, William D.; Spencer, Shawn D.; Raffeld, Mark; Decker, Jean R.; Goldman, Carolyn K.; Bryant, Bonita R.; Petrus, Michael N.; Creekmore, Stephen P.; Morris, John C.

In: Blood, Vol. 121, No. 3, 17.07.2013, p. 476-484.

Research output: Contribution to journalArticle

Waldmann, TA, Conlon, KC, Stewart, DM, Worthy, TYA, Janik, JE, Fleisher, TA, Albert, PS, Figg, WD, Spencer, SD, Raffeld, M, Decker, JR, Goldman, CK, Bryant, BR, Petrus, MN, Creekmore, SP & Morris, JC 2013, 'Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-Beta-1 mAb in patients with T-cell large granular lymphocytic leukemia', Blood, vol. 121, no. 3, pp. 476-484. https://doi.org/10.1182/blood-2012-08-450585
Waldmann, Thomas A. ; Conlon, Kevin C. ; Stewart, Donn M. ; Worthy, Tat Yana A. ; Janik, John Edward ; Fleisher, Thomas A. ; Albert, Paul S. ; Figg, William D. ; Spencer, Shawn D. ; Raffeld, Mark ; Decker, Jean R. ; Goldman, Carolyn K. ; Bryant, Bonita R. ; Petrus, Michael N. ; Creekmore, Stephen P. ; Morris, John C. / Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-Beta-1 mAb in patients with T-cell large granular lymphocytic leukemia. In: Blood. 2013 ; Vol. 121, No. 3. pp. 476-484.
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AU - Decker, Jean R.

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