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 | |
| State | Published - Jul 17 2013 |
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ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology
Cite this
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
}
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 Edward
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
UR - http://www.scopus.com/inward/citedby.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
VL - 121
SP - 476
EP - 484
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -