Clinical and immunological evaluation of zoledronate-activated Vgamma9gammadelta T-cell-based immunotherapy for patients with multiple myeloma

Exp Hematol. 2009 Aug;37(8):956-68. doi: 10.1016/j.exphem.2009.04.008. Epub 2009 May 4.


Objective: To evaluate the potential anti-tumor activity of zoledronate-activated Vgamma9gammadelta T cells in vivo, we initiated a pilot study involving administration of zoledronate-activated Vgamma9gammadelta 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 Vgamma9gammadelta 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) Vgamma9gammadelta T LAK cells per infusion.

Results: No serious treatment-related adverse effects were observed during the study period. The percentage of Vgamma9gammadelta T cells in PBMCs and absolute numbers of Vgamma9gammadelta T cells in peripheral blood, particularly those of CD45RA(-)CD27(-) effector memory (TEM) Vgamma9gammadelta T-cell subsets increased in all the patients. Percentages of Vgamma9gammadelta T cells and TEM Vgamma9gammadelta 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.

Conclusion: Administration of zoledronate-activated Vgamma9gammadelta T LAK cells is a safe and promising immunotherapy approach for treatment of patients with multiple myeloma.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Blood Cells / cytology
  • Bone Density Conservation Agents / administration & dosage
  • Bone Marrow Cells / cytology
  • Cell Culture Techniques
  • Diphosphonates / administration & dosage*
  • Female
  • Humans
  • Imidazoles / administration & dosage*
  • Immunotherapy, Adoptive / methods*
  • Interleukin-2 / pharmacology
  • Killer Cells, Lymphokine-Activated / immunology
  • Killer Cells, Lymphokine-Activated / transplantation*
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Count
  • Lymphocyte Subsets
  • Male
  • Middle Aged
  • Multiple Myeloma / therapy*
  • Pilot Projects
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Treatment Outcome
  • Zoledronic Acid


  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Interleukin-2
  • Receptors, Antigen, T-Cell, gamma-delta
  • Zoledronic Acid