Anti-myeloma activity of endogenous and adoptively transferred activated natural killer cells in experimental multiple myeloma model

Alici, Evren; Konstantinidis, Kyriakos V.; Sutlu, Tolga; Aints, Alar; Gahrton, Gösta; Ljunggren, Hans-Gustaf; Dilber, M. Sirac

doi:10.1016/j.exphem.2007.08.006

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Volume 35, Issue 12 , Pages 1839-1846, December 2007

Anti-myeloma activity of endogenous and adoptively transferred activated natural killer cells in experimental multiple myeloma model

Evren Alici
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
- Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Kyriakos V. Konstantinidis
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
- Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Tolga Sutlu
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Alar Aints
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
- Present address for Dr. Aints: Division of Hemato-Oncology, Department of Medicine, Tartu University, Tartu, Estonia, and Competence Centre for Cancer Research, Tallinn, Estonia.
Gösta Gahrton
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
Hans-Gustaf Ljunggren
- Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
M. Sirac Dilber
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
- Offprint requests to: Sirac Dilber, M.D., Ph.D., Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden

Received 9 June 2007; received in revised form 31 July 2007; accepted 2 August 2007.

Objective

Despite advances in autologous stem cell transplantation and chemotherapy, multiple myeloma (MM) remains an incurable disease. Due to the role of natural killer (NK) cells in host resistance against several tumors, it is of interest to explore the anti-MM activity of NK cells. For this reason, we aimed to determine if NK cells provide anti-MM activity following interleukin-2 (IL-2) administration, and if ex vivo activated and intravenously administered NK cells prolong survival in MM-bearing C57BL/KaLwRij mice.

Methods

The anti-MM effect of IL-2 was tested by intraperitoneal injection into the 5T33MM-inoculated mice. Subsequently, in vivo effector cell depletions were performed by administration of anti-NK1.1 or anti-CD8 monoclonal antibodies. Finally, magnetically separated and activated NK cells from splenocytes of C57BL/KaLwRij mice were adoptively transferred to tumor-bearing mice in conjunction with IL-2 treatment.

Results

IL-2 administration into MM-bearing mice significantly prolonged their survival. This effect was diminished by in vivo depletion of NK cells. Adoptive transfer of activated NK cells showed a significant in vivo anti-MM effect that was dependent on cell dose. Biodistribution of the marked adoptively transferred NK cells correlated with MM cells' homing sites.