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

doi: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

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

Pulmonary Disease

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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 language	English (US)
Pages (from-to)	476-484
Number of pages	9
Journal	Blood
Volume	121
Issue number	3
DOIs	https://doi.org/10.1182/blood-2012-08-450585
State	Published - Jul 17 2013

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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Waldmann, T. A., Conlon, K. C., Stewart, D. M., Worthy, T. Y. A., Janik, J. E., Fleisher, T. A., Albert, P. S., Figg, W. D., Spencer, S. D., Raffeld, M., Decker, J. R., Goldman, C. K., Bryant, B. R., Petrus, M. N., Creekmore, S. P., & 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 journal › Article › peer-review

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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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.",

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AU - Goldman, Carolyn K.

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