In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma Anti-myeloma activity of amplified gamma delta T cells

• Published in: British journal of haematology Vol. 139; no. 2; pp. 206 - 16
• Main Authors: Burjanadze, Maka, Condomines, Maud, Rème, Thierry, Quittet, Philippe, Latry, Pascal, Lugagne, Cécile, Romagne, François, Morel, Yanis, Rossi, Jean-François, Klein, Bernard, Lu, Zhao-Yang
• Format: Journal Article
• Language: English
• Published: Wiley 01.10.2007
• Subjects: Cancer; Cellular Biology; Hematology; Human health and pathology; Immunology; Life Sciences; multiple myeloma; gamma delta T cells; immunotherapy; cellular therapy; cytotoxicity
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2007.06754.x

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.