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 E. 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 E. 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

^*Corresponding author for this work

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

59 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
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 - 17 Jul 2013
Externally published	Yes

Access to Document

10.1182/blood-2012-08-450585

Cite this

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

@article{c0edfc477d1a499e86df558d54aef8aa,

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

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.",

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

year = "2013",

month = jul,

day = "17",

doi = "10.1182/blood-2012-08-450585",

language = "English",

volume = "121",

pages = "476--484",

journal = "Blood",

issn = "0006-4971",

number = "3",

}

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

TY - JOUR

T1 - Phase 1 trial of IL-15 trans presentation blockade using humanized Mik-Beta-1 mAb in patients with T-cell large granular lymphocytic leukemia

AU - Waldmann, Thomas A.

AU - Conlon, Kevin C.

AU - Stewart, Donn M.

AU - Worthy, Tat Yana A.

AU - Janik, John E.

AU - Fleisher, Thomas A.

AU - Albert, Paul S.

AU - Figg, William D.

AU - Spencer, Shawn D.

AU - Raffeld, Mark

AU - Decker, Jean R.

AU - Goldman, Carolyn K.

AU - Bryant, Bonita R.

AU - Petrus, Michael N.

AU - Creekmore, Stephen P.

AU - Morris, John C.

PY - 2013/7/17

Y1 - 2013/7/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84872482913&partnerID=8YFLogxK

U2 - 10.1182/blood-2012-08-450585

DO - 10.1182/blood-2012-08-450585

M3 - Article

C2 - 23212516

AN - SCOPUS:84872482913

SN - 0006-4971

VL - 121

SP - 476

EP - 484

JO - Blood

JF - Blood

IS - 3

ER -

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

Abstract

Access to Document

Fingerprint

Cite this