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

Objective. To evaluate the potential anti-tumor activity of zoledronate-activated V gamma 9 gamma delta T cells in vivo, we initiated a pilot study involving administration of zoledronate-activated V gamma 9 gamma delta T lymphocyte-activated killer (LAK) cells to patients with multiple myeloma. Materials and Methods. Subjects (n = 6) received four intravenous infusions at 2-week intervals of zoledronate-activated V gamma 9 gamma delta 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 x 10(9) V gamma 9 gamma delta T LAK cells per infusion. Results. No serious treatment-related adverse effects were observed during the study period. The percentage of V gamma 9 gamma delta T cells in PBMCs and absolute numbers of V gamma 9 gamma delta T cells in peripheral blood, particularly those of CD45RA(-)D27(-) effector memory (TEM) V gamma 9 gamma delta T-cell subsets increased in all the patients. Percentages of V gamma 9 gamma delta T cells and TEM V gamma 9 gamma delta T cells in bone marrow also increased in all the patients so far tested. NI-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. Conclusion. Administration of zoledronate-activated V gamma 9 gamma delta T LAK cells is a safe and promising immunotherapy approach for treatment of patients with multiple myeloma. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.