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

Abe, Yu, Muto, Masato, Nieda, Mie, Nakagawa, Yasunori, Nicol, Andrew, Kaneko, Touru, Goto, Shigenori, Yokokawa, Kiyoshi and Suzuki, Kenshi (2009) Clinical and immunological evaluation of zoledronate-activated Vγ9γδ T-cell-based immunotherapy for patients with multiple myeloma. Experimental Hematology, 37 8: 956-968. doi:10.1016/j.exphem.2009.04.008


Author Abe, Yu
Muto, Masato
Nieda, Mie
Nakagawa, Yasunori
Nicol, Andrew
Kaneko, Touru
Goto, Shigenori
Yokokawa, Kiyoshi
Suzuki, Kenshi
Title Clinical and immunological evaluation of zoledronate-activated Vγ9γδ T-cell-based immunotherapy for patients with multiple myeloma
Journal name Experimental Hematology   Check publisher's open access policy
ISSN 0301-472X
1873-2399
Publication date 2009-08
Sub-type Article (original research)
DOI 10.1016/j.exphem.2009.04.008
Volume 37
Issue 8
Start page 956
End page 968
Total pages 13
Place of publication New York, USA
Publisher Elsevier
Language eng
Subject 1102 Cardiovascular Medicine and Haematology
Formatted abstract
Objective

To 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 Methods


Subjects (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.

Results


No 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.

Conclusion


Administration of zoledronate–activated Vγ9γδ T LAK cells is a safe and promising immunotherapy approach for treatment of patients with multiple myeloma.

Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Thu, 03 Sep 2009, 07:46:09 EST by Mr Andrew Martlew on behalf of Faculty Of Health Sciences