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

Abstract

T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (γδ T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate Vγ9Vδ2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating γδ T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating γδ 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 γδ T cells in 78% of newly diagnosed patients. γδ T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded γδ 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 γδ T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.