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Open AccessArticle

HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM)

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Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan 87159-88141, Iran
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Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 16635-148, Iran
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Department of Radiology Medical Imaging Center, Imam Khomeini Hospital, Tehran 141-9733-141, Iran
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Department of Neurosurgery, Department of Applied Cell Sciences and Trauma Research Center, Kashan University of Medical Sciences, Kashan 87159-88141, Iran
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Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115111, Iran
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Faculty of Science, University of Toronto Scarborough, Toronto, ON M1C 1A4, Canada
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Biotechnology Center, Silesian University of Technology, 44-100 Gliwice, Poland
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LinkoCare Life Sciences AB, 583 30 Linköping, Sweden
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Faculty of Health, York University, Toronto, ON M3J 1P3, Canada
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Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada
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Faculty of Medicine, Katowice School of Technology, 40-555 Katowice, Poland
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Pediatric Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran 1419733151, Iran
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(7), 2263; https://doi.org/10.3390/ijms21072263 (registering DOI)
Received: 26 February 2020 / Revised: 21 March 2020 / Accepted: 22 March 2020 / Published: 25 March 2020
(This article belongs to the Special Issue Recent Advances in Biotechnology)
Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein 70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intracranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2-treated NK cells as compared to those subjected to nontreated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2-treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM. View Full-Text
Keywords: glioblastoma multiforme; rat model; NK cell therapy; MRI cell tracking; fluorescent cell tracking; blood brain barrier glioblastoma multiforme; rat model; NK cell therapy; MRI cell tracking; fluorescent cell tracking; blood brain barrier
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Sharifzad, F.; Mardpour, S.; Mardpour, S.; Fakharian, E.; Taghikhani, A.; Sharifzad, A.; Kiani, S.; Heydarian, Y.; Łos, M.J.; Azizi, Z.; Ghavami, S.; Hamidieh, A.A.; Ebrahimi, M. HSP70/IL-2 Treated NK Cells Effectively Cross the Blood Brain Barrier and Target Tumor Cells in a Rat Model of Induced Glioblastoma Multiforme (GBM). Int. J. Mol. Sci. 2020, 21, 2263.

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