In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma.
T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (gammadelta T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate Vgamma9Vdelta2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating gammadelta T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating gammadelta T cell counts in patients with newly diagnosed MM or in relapse did not differ from those in healthy donors. A 14-d culture of peripheral blood mononuclear cells with Phosphostim and IL-2 triggered a 100-fold expansion of gammadelta T cells in 78% of newly diagnosed patients. Gammadelta T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded gammadelta T cells killed 13/14 myeloma cell lines as well as primary myeloma cells, but not normal CD34 cells. Their killing efficiency was not affected by 2-d IL-2 starvation. This study demonstrated the ability of Phosphostim and IL-2 to expand gammadelta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.
Burjanadzé
Maka
M
INSERM, U847, Montpellier, France.
Condomines
Maud
M
Reme
Thierry
T
Quittet
Philippe
P
Latry
Pascal
P
Lugagne
Cécile
C
Romagne
François
F
Morel
Yanis
Y
Rossi
Jean François
JF
Klein
Bernard
B
Lu
Zhao Yang
ZY
D019264:Adoptive Transfer / Q000379:methods*; D018952:Antigens, CD34 / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D011756:Diphosphates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D018952:Antigens, CD34; D017252:CD3 Complex; D011756:Diphosphates; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019718:Receptors, CXCR4; C429553:bromohydrin pyrophosphate