Publication details
Vdelta1 gamma-delta T cell-mediated killing of myeloma cells: a new candidate for immunotherapy
| Authors | |
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| Year of publication | 2013 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Gamma-delta T cells are potent effector lymphocytes of innate immunity and are involved in anti-tumour immune surveillance. There are two major subsets of gamma-delta T cells in humans; Vdelta1 and Vdelta2 subsets. Each subset recognize tumours by separate mechanisms involving phosphoantigens and stress-induced ligands for the activating receptor NKG2D including MICA/B and UL-16 binding proteins. The Vdelta2 subset is known to recognize Multiple Myeloma (MM) but Vdelta1+ cells targeting MM has not previously been investigated. We have examined the cytotoxic potential of Vdelta1+ cells to lyse myeloma cell lines RPMI8226 and U266, and plasma cell leukaemia ARH77. Vdelta1+ cells were purified from peripheral blood mononuclear cells from healthy donors by immunomagnetic sorting and expanded (purity of 95-97%) over 3 weeks on irradiated PBMC. Vdelta1+ cells were co-cultured with target cell lines at 5:1 and 10:1 E:T ratio in a 4-hour flow cytometric killing assay. The expanded Vdelta1+ cells showed prominent anti-myeloma reactivity by specific lysis against all three cell lines, with the highest lysis of U266 cells (mean 73.23%, SD 11.9). Vdelta1+ cells isolated from peripheral blood of myeloma patient also showed high cytotoxic reactivity of 71.6% against U266 cells. Vdelta2+ gamma-delta T cell-mediated lysis was not significantly different to lysis by Vdelta1+ cells (mean 64.13%, SD 9.3). Multiple Myeloma remains incurable and most patients relapse or become resistant to conventional treatment. Our results identify myeloma-reactive Vdelta1+ gamma-delta T cells as promising candidates for a novel tumour immunotherapy. |