Impact of the immunomodulating peptide thymosin alpha 1 on multiple myeloma and immune recovery after hematopoietic stem cell transplantation

被引:3
作者
Binsfeld, Marilene [1 ]
Hannon, Muriel [1 ]
Otjacques, Eleonore [1 ]
Humblet-Baron, Stephanie [2 ]
Baudoux, Etienne [3 ,4 ]
Beguin, Yves [1 ,3 ,4 ]
Baron, Frederic [1 ]
Caers, Jo [1 ]
机构
[1] Univ Liege, Hematol Lab, GIGA Res, CHU Liege, B-4000 Liege, Belgium
[2] Katholieke Univ Leuven, Lab Genet Autoimmun, B-3000 Louvain, Belgium
[3] Univ Liege, Lab Cell & Gene Therapy, B-4000 Liege, Belgium
[4] CHU Liege, B-4000 Liege, Belgium
关键词
Multiple myeloma; Thymosin alpha 1; Hematopoietic stem cell transplantation; Immune recovery; IN-VITRO; THYMOSIN-ALPHA(1); INTERLEUKIN-2; CANCER; CHEMOIMMUNOTHERAPY; 5-FLUOROURACIL; COMBINATION; EXPRESSION; RESISTANCE; EFFICACY;
D O I
10.1007/s00262-015-1708-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Multiple myeloma (MM) is characterized by the accumulation of monoclonal plasma cells in the bone marrow and causes several immune alterations in patients. Thymosin alpha 1 (T alpha 1) is a thymic peptide that has been associated with immuno-stimulating properties. In addition, this peptide exerts anti-tumor effects in several cancer types. Beneficial effects of T alpha 1 administration have also been shown on immune reconstitution after hematopoietic stem cell transplantation (HSCT), a current treatment modality in hematological malignancies including MM. In this study, we observed a slight reduction in the proliferation of murine and human MM cell lines in the presence of T alpha 1 in vitro. However, using two immunocompetent murine MM models (5TGM1 and MOPC315.BM), we did not observe any impact of T alpha 1 administration on MM development in vivo. Furthermore, no beneficial effects of T alpha 1 treatment were observed on lymphocyte immune reconstitution after transfusion of human hematopoietic stem cells into immunodeficient mice. In conclusion, despite direct effects of T alpha 1 on human MM cell line proliferation in vitro, T alpha 1 did not exert anti-myeloma effects in vivo in the two murine models tested. Moreover, T alpha 1 failed to improve immune recovery in a xenogeneic HSCT model.
引用
收藏
页码:989 / 998
页数:10
相关论文
共 36 条
[1]   Thymosin alpha(1) antagonizes dexamethasone and CD3-induced apoptosis of CD4(+)CD8(+) thymocytes through the activation of cAMP and protein kinase C dependent second messenger pathways [J].
Baumann, CA ;
Badamchian, M ;
Goldstein, AL .
MECHANISMS OF AGEING AND DEVELOPMENT, 1997, 94 (1-3) :85-101
[2]   Cellular immunotherapy in multiple myeloma: Lessons from preclinical models [J].
Binsfeld, M. ;
Fostier, K. ;
Muller, J. ;
Baron, F. ;
Schots, R. ;
Beguin, Y. ;
Heusschen, R. ;
Caers, J. .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2014, 1846 (02) :392-404
[3]   Establishment of a Murine Graft-versus-Myeloma Model Using Allogeneic Stem Cell Transplantation [J].
Binsfeld, Marilene ;
Beguin, Yves ;
Belle, Ludovic ;
Otjacques, Eleonore ;
Hannon, Muriel ;
Briquet, Alexandra ;
Heusschen, Roy ;
Drion, Pierre ;
Zilberberg, Jenny ;
Bogen, Bjarne ;
Baron, Frederic ;
Caers, Jo .
PLOS ONE, 2014, 9 (11)
[4]   Thymosin α1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo [J].
Bozza, Silvia ;
Gaziano, Roberta ;
Bonifazi, Pierluigi ;
Zelante, Teresa ;
Pitzurra, Lucia ;
Montagnoli, Claudia ;
Moretti, Silvia ;
Castronari, Roberto ;
Sinibaldi, Paola ;
Rasi, Guido ;
Garaci, Enrico ;
Bistoni, Francesco ;
Romani, Luigina .
INTERNATIONAL IMMUNOLOGY, 2007, 19 (11) :1261-1270
[5]  
Bubeník J, 2004, INT J ONCOL, V25, P487
[6]   Multiple myeloma - an update on diagnosis and treatment [J].
Caers, Jo ;
Broek, Isabelle Vande ;
De Raeve, Hendrik ;
Michaux, Lucienne ;
Trullemans, Fabienne ;
Schots, Rik ;
Van Camp, Ben ;
Vanderkerken, Karin .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2008, 81 (05) :329-343
[7]   Primary antitumor immune response mediated by CD4+ T cells [J].
Corthay, A ;
Skovseth, DK ;
Lundin, KU ;
Rosjo, E ;
Omholt, H ;
Hofgaard, PO ;
Haraldsen, G ;
Bogen, B .
IMMUNITY, 2005, 22 (03) :371-383
[8]   The role of Tα1 on the infective patients after hematopoietic stem cell transplantation [J].
Ding, Jia-Hua ;
Wang, Lin-Lin ;
Chen, Zhi ;
Wang, Jun ;
Yu, Zheng-Ping ;
Zhao, Gang ;
Chen, Bao-An .
INTERNATIONAL JOURNAL OF HEMATOLOGY, 2013, 97 (02) :280-283
[9]  
FAVALLI C, 1985, CANCER IMMUNOL IMMUN, V20, P189
[10]   A murine model of human myeloma bone disease [J].
Garrett, IR ;
Dallas, S ;
Radl, J ;
Mundy, GR .
BONE, 1997, 20 (06) :515-520