Clinical and immunological evaluation of zoledronate-activated Vγ9γδ T-cell-based immunotherapy for patients with multiple myeloma

ObjectiveTo evaluate the potential anti-tumor activity of zoledronate-activated Vγ9γδ T cells in vivo, we initiated a pilot study involving administration of zoledronate-activated Vγ9γδ T lymphocyte-activated killer (LAK) cells to patients with multiple myeloma.Materials and MethodsSubjects (n = 6) received four intravenous infusions at 2-week intervals of zoledronate-activated Vγ9γδ T LAK cells generated from the culture of peripheral blood mononuclear cells (PBMCs) in the presence of zoledronate and interleukin-2. If the M-protein level in the patient's serum remained at baseline following four intravenous infusions, the patient underwent four more treatments at 4-week intervals. Subjects (n = 6) received a median of 0.99 × 109 Vγ9γδ T LAK cells per infusion.ResultsNo serious treatment-related adverse effects were observed during the study period. The percentage of Vγ9γδ T cells in PBMCs and absolute numbers of Vγ9γδ T cells in peripheral blood, particularly those of CD45RA−CD27− effector memory (TEM) Vγ9γδ T-cell subsets increased in all the patients. Percentages of Vγ9γδ T cells and TEM Vγ9γδ T cells in bone marrow also increased in all the patients so far tested. M-protein levels in the serum remained at baseline in four of six patients and increased in two of six patients. Soluble major histocompatibility complex class I chain-related antigen A was detected only in the serum of patients whose M-protein level increased.ConclusionAdministration of zoledronate–activated Vγ9γδ T LAK cells is a safe and promising immunotherapy approach for treatment of patients with multiple myeloma.