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

Summary 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.