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Low Dose Focused Ultrasound Induces Enhanced Tumor Accumulation of Natural Killer Cells

Sta Maria, Naomi S. and Barnes, Samuel R. and Weist, Michael R. and Colcher, David and Raubitschek, Andrew A. and Jacobs, Russell E. (2015) Low Dose Focused Ultrasound Induces Enhanced Tumor Accumulation of Natural Killer Cells. PLoS ONE, 10 (11). Art. No. e0142767. ISSN 1932-6203. PMCID PMC4640510. https://resolver.caltech.edu/CaltechAUTHORS:20151116-112120972

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[img] MS Excel (S1 Dataset. Apparent Diffusion Coefficient Data) - Supplemental Material
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[img] MS Excel (S2 Dataset. ΔR2* Data for ldbFUS/0.25MPa Group) - Supplemental Material
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[img] MS Excel (S4 Dataset. Data for Histological Quantification of % NK Cell Counts) - Supplemental Material
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Abstract

Natural killer (NK) cells play a vital antitumor role as part of the innate immune system. Efficacy of adoptive transfer of NK cells depends on their ability to recognize and target tumors. We investigated whether low dose focused ultrasound with microbubbles (ldbFUS) could facilitate the targeting and accumulation of NK cells in a mouse xenograft of human colorectal adenocarcinoma (carcinoembryonic antigen (CEA)-expressing LS-174T implanted in NOD.Cg-Prkdc^(scid)Il2rg^(tm1Wjl)/SzJ (NSG) mice) in the presence of an anti-CEA immunocytokine (ICK), hT84.66/M5A-IL-2 (M5A-IL-2). Human NK cells were labeled with an FDA-approved ultra-small superparamagnetic iron oxide particle, ferumoxytol. Simultaneous with the intravenous injection of microbubbles, focused ultrasound was applied to the tumor. In vivo longitudinal magnetic resonance imaging (MRI) identified enhanced accumulation of NK cells in the ensonified tumor, which was validated by endpoint histology. Significant accumulation of NK cells was observed up to 24 hrs at the tumor site when ensonified with 0.50 MPa peak acoustic pressure ldbFUS, whereas tumors treated with at 0.25 MPa showed no detectable NK cell accumulation. These clinically translatable results show that ldbFUS of the tumor mass can potentiate tumor homing of NK cells that can be evaluated non-invasively using MRI.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.pone.0142767DOIArticle
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142767PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640510/PubMed CentralArticle
ORCID:
AuthorORCID
Barnes, Samuel R.0000-0002-1065-8442
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2015 Sta Maria et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: July 8, 2015; Accepted: October 27, 2015; Published: November 10, 2015. This work was supported by the National Institutes of Health (EB000993) (http://www.nibib.nih.gov/) and the Beckman Institute at Caltech (http://www.beckmaninstitute.caltech.edu/) to REJ; and National Institutes of Health (CA43904) (http://www.cancer.gov/) and the Beckman Institute at the City of Hope (http://www.cityofhope.org/beckman-researchinstitute) to DC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors acknowledge the contributions of Sharon Lin for invaluable assistance with animal and cell based work, of Xiaowei Zhang and Thomas Ng for MRI expertise. The authors would also like to thank Desiree Crow, Junie Chea, Sarah McCaig, Xui-Li Li, Jianyi Wang, Anakim Sherman, Kofi Poku and Mark Sherman from City of Hope, for excellent contributions with NK cell generation and expansion, tumor induction, and constructing the immunocytokine product. Also the authors would like to thank Nathan Dalleska, from the Caltech Environmental Analysis Center, for his help collecting the ICP-MS data. Author Contributions: Conceived and designed the experiments: REJ AAR DC NSSM. Performed the experiments: NSSM SRB MW REJ. Analyzed the data: NSSMSRBMWREJ. Contributed eagents/materials/analysis tools: DC AAR REJ. Wrote the paper: NSSM SRB MW DC AAR REJ.
Funders:
Funding AgencyGrant Number
National Institute of Biomedical Imaging and BioengineeringEB000993
Caltech Beckman InstituteUNSPECIFIED
National Cancer InstituteCA43904
City of HopeUNSPECIFIED
Issue or Number:11
PubMed Central ID:PMC4640510
Record Number:CaltechAUTHORS:20151116-112120972
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20151116-112120972
Official Citation:Sta Maria NS, Barnes SR, Weist MR, Colcher D, Raubitschek AA, Jacobs RE (2015) Low Dose Focused Ultrasound Induces Enhanced Tumor Accumulation of Natural Killer Cells. PLoS ONE 10 (11): e0142767. doi:10.1371/journal.pone.0142767
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:62124
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:17 Nov 2015 23:36
Last Modified:09 Mar 2020 13:18

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