Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components

被引:157
作者
Alici, Evren [1 ,2 ]
Sutlu, Tolga [1 ]
Boejrkstrand, Bo [1 ]
Gilljam, Mari [1 ]
Stellan, Birgitta [1 ]
Nahi, Hareth [1 ]
Quezada, Hernan Concha [1 ,2 ]
Gahrton, Goesta [1 ]
Ljunggren, Hans-Gustaf [2 ]
Dilber, M. Sirac [1 ]
机构
[1] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Med, SE-14186 Stockholm, Sweden
[2] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Ctr Infect Med,Dept Med, Stockholm, Sweden
关键词
D O I
10.1182/blood-2007-09-110312
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Multiple myeloma (MM) is an incurable plasma cell malignancy with poor outcome. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy, and immunotherapy. Cell-based immunotherapy after hematopoietic stem-cell transplantation has been attempted, but with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied. Here, we explored the possibility of expanding NK cells from the peripheral blood of 7 newly diagnosed, untreated MM patients, using good manufacturing practice (GMP)compliant components. After 20 days of culture, the number of NK cells from these patients had expanded on average 1600-fold. Moreover, expanded NK cells showed significant cytotoxicity against primary autologous MM cells, yet retained their tolerance against nonmalignant cells. Based on these findings, we propose that autologous NK cells expanded ex vivo deserve further attention as a possible new treatment modality for MM.
引用
收藏
页码:3155 / 3162
页数:8
相关论文
共 46 条
[1]   Long-term follow-up of gene-marked CD34+ cells after autologous stem cell transplantation for multiple myeloma [J].
Alici, E. ;
Bjorkstrand, B. ;
Treschow, A. ;
Aints, A. ;
Smith, C. I. E. ;
Gahrton, G. ;
Dilber, M. S. .
CANCER GENE THERAPY, 2007, 14 (03) :227-232
[2]   CD107a as a functional marker for the identification of natural killer cell activity [J].
Alter, G ;
Malenfant, JM ;
Altfeld, M .
JOURNAL OF IMMUNOLOGICAL METHODS, 2004, 294 (1-2) :15-22
[3]   In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma [J].
Beyer, Marc ;
Kochanek, Matthias ;
Giese, Thomas ;
Endl, Elmar ;
Weihrauch, Martin R. ;
Knolle, Percy A. ;
Classen, Sabine ;
Schultze, Joachim L. .
BLOOD, 2006, 107 (10) :3940-3949
[4]  
BIANCHI A, 1991, HAEMATOLOGICA, V76, P383
[5]   Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-β1 and interleukin-10 [J].
Brown, RD ;
Pope, B ;
Murray, A ;
Esdale, W ;
Sze, DM ;
Gibson, J ;
Ho, PJ ;
Hart, D ;
Joshua, D .
BLOOD, 2001, 98 (10) :2992-2998
[6]   Activation, coactivation, and costimulation of resting human natural killer cells [J].
Bryceson, Yenan T. ;
March, Michael E. ;
Ljunggren, Hans-Gustaf ;
Long, Eric O. .
IMMUNOLOGICAL REVIEWS, 2006, 214 :73-91
[7]   Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion [J].
Bryceson, YT ;
March, ME ;
Ljunggren, HG ;
Long, EO .
BLOOD, 2006, 107 (01) :159-166
[8]   HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells [J].
Carbone, E ;
Neri, P ;
Mesuraca, M ;
Fulciniti, MT ;
Otsuki, T ;
Pende, D ;
Groh, V ;
Spies, T ;
Pollio, G ;
Cosman, D ;
Catalano, L ;
Tassone, P ;
Rotoli, B ;
Venuta, S .
BLOOD, 2005, 105 (01) :251-258
[9]   A new method for in vitro expansion of cytotoxic human CD3-CD56+ natural killer cells [J].
Carlens, S ;
Gilljam, M ;
Chambers, BJ ;
Aschan, J ;
Guven, H ;
Ljunggren, HG ;
Christensson, B ;
Dilber, MS .
HUMAN IMMUNOLOGY, 2001, 62 (10) :1092-1098
[10]   DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells [J].
Carlsten, Mattias ;
Bjorkstrom, Niklas K. ;
Norell, Hakan ;
Bryceson, Yenan ;
van Hall, Thorbald ;
Baumann, Bettina C. ;
Hanson, Mikael ;
Schedvins, Kjell ;
Kiessling, Rolf ;
Ljunggren, Hans-Gustaf ;
Malmberg, Karl Johan .
CANCER RESEARCH, 2007, 67 (03) :1317-1325