Short Title:
NK cells CM
Responsible HRP Element:
Human Health Countermeasures
Funding Status:
Active - Currently funded and in progress
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Procurement Mechanism(s):
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Aims:
SA1: Determine the effect of simulated microgravity on the anti-tumor capacity of human NK-cells and γδ-T cells in vivo.
Experimental Approach: We will use our established rotating cell culture model to expose human PBMCs, expanded NK-cells or
expanded γδ-T cells to simulated microgravity or controls (static-1G and rotational control) prior to adoptive transfer into human
tumor bearing NOD-scid-IL2Rγnull (NSG) mice. The NSG mice will be engrafted with a human luciferase-labelled human leukemia
cell line (K562), as blood cancers are considered a risk for long duration exploration crew. The NSG mice will also be engrafted with
an NK-cell sensitive solid tumor (human neuroblastoma; SK-N-SH cell line) which will enable us to study tumor infiltrates by isolating
tissues and quantifying the human immune cells in the tumor by multi-parameter flow cytometry. Spectral imaging (LagoX) will be
utilized to measure tumor progression and dissemination of the luciferase-tagged human cancer cell lines. Hypothesis: Exposure to
simulated microgravity will have an adverse effect on the in vivo dynamics of human NK and γδ-T cells, impairing their ability to
infiltrate and control human tumor growth in a humanized rodent model.
SA2: Determine the effect of systemic administration of IL-2 and ZOL on the function of NK and γδ-T cells respectively. Experimental
Approach: NSG mice adoptively transferred with human PBMCs, NK-cells and γδ-T cells will be infused with zoledronic acid (ZOL)
and IL-2 as a potential countermeasure to microgravity-induced immune system impairment. ZOL and IL-2 are currently used
clinically to increase the proliferation and function of NK-cells and γδ-T cells in bone marrow transplant patients to prevent disease
relapse. Hypothesis: Systemic administration of IL-2 and ZOL will ‘rescue’ the in vivo anti-tumor activity of human NK-cells and γδ-T
cells following their exposure to simulated microgravity.
Other Resources
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Yes
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Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Annual report and Final reports
Internal Customers:
None
External Customers:
None