Increased effect of IMiDs by addition of cytokine-induced killer cells in multiple myeloma

被引:5
作者
Bullok, Katharina F. [1 ]
Sippel, Christoph [1 ]
Schmidt-Wolf, Ingo G. H. [1 ]
机构
[1] Univ Klinikum Bonn, Ctr Integrated Oncol, Sigmund Freud Str 25, D-53105 Bonn, Germany
关键词
multiple myeloma; cytokine-induced killer cells; immunomodulatory drugs; immunotherapy; IMMUNOMODULATORY DRUGS; T-CELLS; LENALIDOMIDE; POMALIDOMIDE; THALIDOMIDE; THERAPY; DEXAMETHASONE; ACTIVATION; SUBSET;
D O I
10.1002/hon.2200
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide and pomalidomide, represent the basic principle of multiple myeloma treatment. However, the development of resistance is a limiting factor. Over the last years, the efficient application of cytokine-induced killer (CIK) cells has been reported as an alternative strategy to treat hematological neoplasms. In this study, we tested for a potential synergistic effect by combining the IMiDs thalidomide, lenalidomide and pomalidomide with CIK cells in different myeloma cell lines in vitro. Myeloma cells tested with CIK cells were significantly reduced. In the combination, myeloma cells were significantly reduced compared with cells only tested with IMiDs but not to the cells tested with CIK cells. Otherwise, the number of CIK cells was significantly reduced when treated with IMiDs. Because IMiDs are active in patients with myeloma, these results lead to the expectation that combination of IMiDs and CIK cells achieve better results in the treatment of multiple myeloma compared with the single use of IMiDs. Therefore, further examinations in an in vivo setting are necessary to have a closer look on the cellular interactions. Copyright (c) 2015 John Wiley & Sons, Ltd.
引用
收藏
页码:208 / 216
页数:9
相关论文
共 26 条
[1]   Increased effect of IMiDs by addition of cytokine-induced killer cells in multiple myeloma [J].
Bullok, Katharina F. ;
Sippel, Christoph ;
Schmidt-Wolf, Ingo G. H. .
HEMATOLOGICAL ONCOLOGY, 2016, 34 (04) :208-216
[2]   Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications [J].
Chang, David H. ;
Liu, Nancy ;
Klimek, Virginia ;
Hassoun, Hani ;
Mazumder, Amitabha ;
Nimer, Stephen D. ;
Jagannath, Sundar ;
Dhodapkar, Madhav V. .
BLOOD, 2006, 108 (02) :618-621
[3]   Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN [J].
Gandhi, Anita K. ;
Kang, Jian ;
Havens, Courtney G. ;
Conklin, Thomas ;
Ning, Yuhong ;
Wu, Lei ;
Ito, Takumi ;
Ando, Hideki ;
Waldman, Michelle F. ;
Thakurta, Anjan ;
Klippel, Anke ;
Handa, Hiroshi ;
Daniel, Thomas O. ;
Schafer, Peter H. ;
Chopra, Rajesh .
BRITISH JOURNAL OF HAEMATOLOGY, 2014, 164 (06) :811-821
[4]   Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients [J].
Gay, Francesca ;
Hayman, Suzanne R. ;
Lacy, Martha Q. ;
Buadi, Francis ;
Gertz, Morie A. ;
Kumar, Shaji ;
Dispenzieri, Angela ;
Mikhael, Joseph R. ;
Bergsagel, P. Leif ;
Dingli, David ;
Reeder, Craig B. ;
Lust, John A. ;
Russell, Stephen J. ;
Roy, Vivek ;
Zeldenrust, Steven R. ;
Witzig, Thomas E. ;
Fonseca, Rafael ;
Kyle, Robert A. ;
Greipp, Philip R. ;
Stewart, A. Keith ;
Rajkumar, S. Vincent .
BLOOD, 2010, 115 (07) :1343-1350
[5]   USE OF MTT COLORIMETRIC ASSAY TO MEASURE CELL ACTIVATION [J].
GERLIER, D ;
THOMASSET, N .
JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 94 (1-2) :57-63
[6]   Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma [J].
Goerguen, Guellue ;
Calabrese, Elisabetta ;
Soydan, Ender ;
Hideshima, Teru ;
Perrone, Giulia ;
Bandi, Madhavi ;
Cirstea, Diana ;
Santo, Loredana ;
Hu, Yiguo ;
Tai, Yu-Tzu ;
Nahar, Sabikun ;
Mimura, Naoya ;
Fabre, Claire ;
Raje, Noopur ;
Munshi, Nikhil ;
Richardson, Paul ;
Anderson, Kenneth C. .
BLOOD, 2010, 116 (17) :3227-3237
[7]   Significantly reduced regulatory T cell population in patients with untreated multiple myeloma [J].
Gupta, Ritu ;
Ganeshan, Prasanth ;
Hakim, Mrinali ;
Verma, Rakesh ;
Sharma, Atul ;
Kumar, Lalit .
LEUKEMIA RESEARCH, 2011, 35 (07) :874-878
[8]   Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset [J].
Haslett, PAJ ;
Corral, LG ;
Albert, M ;
Kaplan, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (11) :1885-1892
[9]   Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application [J].
Hayashi, T ;
Hideshima, T ;
Akiyama, M ;
Podar, K ;
Yasui, H ;
Raje, N ;
Kumar, S ;
Chauhan, D ;
Treon, SP ;
Richardson, P ;
Anderson, KC .
BRITISH JOURNAL OF HAEMATOLOGY, 2005, 128 (02) :192-203
[10]   Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC) [J].
Hontscha, C. ;
Borck, Y. ;
Zhou, H. ;
Messmer, D. ;
Schmidt-Wolf, I. G. H. .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2011, 137 (02) :305-310