title: Low Dose Focused Ultrasound Induces Enhanced Tumor Accumulation of Natural Killer Cells.
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-PrkdcscidIl2rgtm1Wjl/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.
authors.affiliation: Division of Biology and Biological Engineering, Beckman Institute, California Institute of Technology, Pasadena, CA, United States of America.
authors.forename: Naomi S
authors.initials: NS
authors.lastname: Sta Maria
authors.affiliation: Division of Biology and Biological Engineering, Beckman Institute, California Institute of Technology, Pasadena, CA, United States of America.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Barnes
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Institute, City of Hope, Duarte, CA, United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Weist
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Institute, City of Hope, Duarte, CA, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Colcher
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Institute, City of Hope, Duarte, CA, United States of America.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Raubitschek
authors.affiliation: Division of Biology and Biological Engineering, Beckman Institute, California Institute of Technology, Pasadena, CA, United States of America.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Jacobs
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D064593:Heterografts; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D006801:Humans; D007694:Killer Cells, Natural; D051379:Mice; D016688:Mice, Inbred NOD; D045423:Microbubbles / Q000627:therapeutic use*; D009368:Neoplasm Transplantation
chemical_list: D002272:Carcinoembryonic Antigen