Selective killing of candidate AML stem cells by antibody targeting of IL1RAP

被引:102
作者
Askmyr, Maria [1 ]
Agerstam, Helena [1 ]
Hansen, Nils [1 ]
Gordon, Sandra [1 ]
Arvanitakis, Alexandros [1 ]
Rissler, Marianne [1 ]
Juliusson, Gunnar [2 ,3 ]
Richter, Johan [4 ,5 ]
Jaras, Marcus [1 ]
Fioretos, Thoas [1 ]
机构
[1] Lund Univ, Univ & Reg Labs, Dept Clin Genet, SE-22184 Lund, Sweden
[2] Lund Univ, Stem Cell Ctr, SE-22184 Lund, Sweden
[3] Skane Univ Hosp, Dept Hematol & Coagulat, Lund, Sweden
[4] Lund Univ, Dept Mol Med & Gene Therapy, SE-22184 Lund, Sweden
[5] Skane Univ Hosp, Dept Hematol & Coagulat, Lund, Sweden
基金
瑞典研究理事会;
关键词
ACUTE MYELOBLASTIC-LEUKEMIA; RECEPTOR ACCESSORY PROTEIN; MYELOID-LEUKEMIA; INTERLEUKIN-1; PROLIFERATION; ANTAGONIST; MODULATION; EXPRESSION;
D O I
10.1182/blood-2012-09-458935
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
IL1RAP, a co-receptor for interleukin (IL)-1 and IL-33 receptors, was previously found to be highly upregulated on candidate chronic myeloid leukemia stem cells, allowing for leukemia-selective killing using IL1RAP-targeting antibodies. We analyzed IL1RAP expression in a consecutive series of 29 patients with acute myeloid leukemia (AML) and, based on the level of expression in mononuclear cells (MNCs), we divided the samples into 3 groups: IL1RAP low (n = 6), IL1RAP intermediate (n = 11), and IL1RAP high (n 5 12). Within the CD34+CD38- population, the intermediate and high groups expressed higher levels of IL1RAP than did corresponding normal cells. With the aim to target AML stem cells, an anti-IL1RAP monoclonal antibody was generated followed by isotype switching for improved antibody-dependent, cell-mediated cytotoxicity activity. Using this antibody, we achieved selective killing of AML MNC, CD34+CD38+, and CD34+CD38- cells. Our findings demonstrate that IL1RAP is a promising new therapeutic target in AML.
引用
收藏
页码:3709 / 3713
页数:5
相关论文
共 11 条
[1]   Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS [J].
Barreyro, Laura ;
Will, Britta ;
Bartholdy, Boris ;
Zhou, Li ;
Todorova, Tihomira I. ;
Stanley, Robert F. ;
Ben-Neriah, Susana ;
Montagna, Cristina ;
Parekh, Samir ;
Pellagatti, Andrea ;
Boultwood, Jacqueline ;
Paietta, Elisabeth ;
Ketterling, Rhett P. ;
Cripe, Larry ;
Fernandez, Hugo F. ;
Greenberg, Peter L. ;
Tallman, Martin S. ;
Steidl, Christian ;
Mitsiades, Constantine S. ;
Verma, Amit ;
Steidl, Ulrich .
BLOOD, 2012, 120 (06) :1290-1298
[2]   Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].
Bonnet, D ;
Dick, JE .
NATURE MEDICINE, 1997, 3 (07) :730-737
[3]   Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases [J].
Dinarello, Charles A. ;
Simon, Anna ;
van der Meer, Jos W. M. .
NATURE REVIEWS DRUG DISCOVERY, 2012, 11 (08) :633-652
[4]   Immunological and Inflammatory Functions of the Interleukin-1 Family [J].
Dinarello, Charles A. .
ANNUAL REVIEW OF IMMUNOLOGY, 2009, 27 :519-550
[5]   Stem cell gene expression programs influence clinical outcome in human leukemia [J].
Eppert, Kolja ;
Takenaka, Katsuto ;
Lechman, Eric R. ;
Waldron, Levi ;
Nilsson, Bjoern ;
van Galen, Peter ;
Metzeler, Klaus H. ;
Poeppl, Armando ;
Ling, Vicki ;
Beyene, Joseph ;
Canty, Angelo J. ;
Danska, Jayne S. ;
Bohlander, Stefan K. ;
Buske, Christian ;
Minden, Mark D. ;
Golub, Todd R. ;
Jurisica, Igor ;
Ebert, Benjamin L. ;
Dick, John E. .
NATURE MEDICINE, 2011, 17 (09) :1086-U91
[6]   INHIBITION OF ACUTE MYELOGENOUS LEUKEMIA BLAST PROLIFERATION BY INTERLEUKIN-1 (IL-1) RECEPTOR ANTAGONIST AND SOLUBLE IL-1 RECEPTORS [J].
ESTROV, Z ;
KURZROCK, R ;
ESTEY, E ;
WETZLER, M ;
FERRAJOLI, A ;
HARRIS, D ;
BLAKE, M ;
GUTTERMAN, JU ;
TALPAZ, M .
BLOOD, 1992, 79 (08) :1938-1945
[7]   Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein [J].
Jaras, Marcus ;
Johnels, Petra ;
Hansen, Nils ;
Agerstam, Helena ;
Tsapogas, Panagiotis ;
Rissler, Marianne ;
Lassen, Carin ;
Olofsson, Tor ;
Bjerrum, Ole Weis ;
Richter, Johan ;
Fioretos, Thoas .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (37) :16280-16285
[8]  
RAMBALDI A, 1991, BLOOD, V78, P3248
[9]   Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice [J].
Sarry, Jean-Emmanuel ;
Murphy, Kathleen ;
Perry, Robin ;
Sanchez, Patricia V. ;
Secreto, Anthony ;
Keefer, Cathy ;
Swider, Cezary R. ;
Strzelecki, Anne-Claire ;
Cavelier, Cindy ;
Recher, Christian ;
Mansat-De Mas, Veronique ;
Delabesse, Eric ;
Danet-Desnoyers, G. ;
Carroll, Martin .
JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (01) :384-395
[10]   MODULATION OF ACUTE MYELOBLASTIC-LEUKEMIA (AML) CELL-PROLIFERATION AND BLAST COLONY FORMATION BY ANTISENSE OLIGOMER FOR IL-1-BETA CONVERTING-ENZYME (ICE) AND IL-1 RECEPTOR ANTAGONIST (IL-1RA) [J].
STOSICGRUJICIC, S ;
BASARA, N ;
MILENKOVIC, P ;
DINARELLO, CA .
JOURNAL OF CHEMOTHERAPY, 1995, 7 (01) :67-70