Task The impact of simulated microgravity on the anti-tumor properties of human NK-cells and ?d-T cells in vivo: IL-2 and zoledronic acid therapy as a potential countermeasure
Last Published:  07/30/21 01:05:34 PM (Central)
Short Title: NK cells CM
Responsible HRP Element: Human Health Countermeasures
Collaborating Org(s):
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
Solicited
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. 
Mappings
RiskRisk of Adverse Health Event Due to Altered Immune Response
You are here!TaskThe impact of simulated microgravity on the anti-tumor properties of human NK-cells and ?d-T cells in vivo: IL-2 and zoledronic acid therapy as a potential countermeasure