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; Suzuki, Kenshi

doi:10.1016/j.exphem.2009.04.008

« Previous Next »Experimental Hematology
Volume 37, Issue 8 , Pages 956-968, August 2009

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

Yu Abe
- Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan
Masato Muto
- Medinet Medical Institute, Tokyo, Japan
Mie Nieda
- Medinet Medical Institute, Tokyo, Japan
- Offprint requests to: Mie Nieda, Ph.D., Medinet Medical Institute, 2-2-8 Tamagawadai, Setagaya-ku, Tokyo 158-0096, Japan
Yasunori Nakagawa
- Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan
Andrew Nicol
- Centre for Immune and Targeted Therapy, University of Queensland, Greenslopes Private Hospital, Brisbane, Australia
Touru Kaneko
- Seta Clinic Group, Tokyo, Japan
Shigenori Goto
- Seta Clinic Group, Tokyo, Japan
Kiyoshi Yokokawa
- Medinet Co. Ltd, Tokyo, Japan
Kenshi Suzuki
- Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan

Received 18 September 2008; received in revised form 23 April 2009; accepted 23 April 2009. published online 01 May 2009.

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.