title: Phase 1 trial of IL-15 trans presentation blockade using humanized Mikβ1 mAb in patients with T-cell large granular lymphocytic leukemia.
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.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA. tawald@helix.nih.gov
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Conlon
authors.forename: Donn M
authors.initials: DM
authors.lastname: Stewart
authors.forename: TatYana A
authors.initials: TA
authors.lastname: Worthy
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Shawn D
authors.initials: SD
authors.lastname: Spencer
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Jean R
authors.initials: JR
authors.lastname: Decker
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: Goldman
authors.forename: Bonita R
authors.initials: BR
authors.lastname: Bryant
authors.forename: Michael N
authors.initials: MN
authors.lastname: Petrus
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Creekmore
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000276:immunology*; D054066:Leukemia, Large Granular Lymphocytic / Q000276:immunology* / Q000628:therapy*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D053646:Interleukin-2 Receptor beta Subunit; D012333:RNA, Messenger