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Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
Published on: October 30, 2016
Anti-myeloma activity of endogenous and adoptively transferred activated natural killer cells in experimental
Evren Alici1, Kyriakos V Konstantinidis, Tolga Sutlu
1Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
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.
Conclusion:
These data suggest that activated NK cells have a promising potential in adoptive immunotherapy for MM.
Insights
Activated natural killer (NK) cells show promise for multiple myeloma (MM) treatment. Adoptive transfer of activated NK cells, combined with interleukin-2 (IL-2), significantly prolonged survival in MM-bearing mice.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Multiple myeloma (MM) remains incurable despite current treatments.
- Natural killer (NK) cells play a role in anti-tumor immunity.
- The potential of NK cells in treating MM requires further investigation.
Purpose of the Study:
- To evaluate the anti-MM activity of NK cells following interleukin-2 (IL-2) administration.
- To determine if ex vivo activated and intravenously administered NK cells can prolong survival in MM-bearing mice.
Main Methods:
- Interleukin-2 (IL-2) was administered to 5T33MM-inoculated mice.
- In vivo NK cell depletion was performed using anti-NK1.1 antibodies.
- Activated NK cells were adoptively transferred to tumor-bearing mice alongside IL-2 treatment.
Main Results:
- IL-2 administration significantly prolonged survival in MM-bearing mice.
- The survival benefit of IL-2 was reduced by NK cell depletion.
- Adoptive transfer of activated NK cells demonstrated a dose-dependent anti-MM effect in vivo.
Conclusions:
- Activated NK cells hold significant potential for adoptive immunotherapy in multiple myeloma.
- NK cell-based therapies represent a promising avenue for future MM treatment strategies.
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