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


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.


CONCLUSIONS
Administration of zoledronate-activated Vgamma9gammadelta T LAK cells is a safe and promising immunotherapy approach for treatment of patients with multiple myeloma.
Abe
Yu
Y
Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.
Muto
Masato
M
Nieda
Mie
M
Nakagawa
Yasunori
Y
Nicol
Andrew
A
Kaneko
Touru
T
Goto
Shigenori
S
Yokokawa
Kiyoshi
K
Suzuki
Kenshi
K
D000328:Adult; D000368:Aged; D001773:Blood Cells / Q000166:cytology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation*; D008213:Lymphocyte Activation / Q000187:drug effects*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D010865:Pilot Projects; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid