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)

International Journal of Molecular Sciences
Farzaneh SharifzadMarzieh Ebrahimi


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 administra...Continue Reading


Mar 9, 2002·Science·F Ulrich Hartl, Manajit Hayer-Hartl
Apr 30, 2003·Nature Immunology·Christina M Trambas, Gillian M Griffiths
Nov 19, 2004·Nature·Sheila K SinghPeter B Dirks
Jul 26, 2005·Cell Stress & Chaperones·Daniel R Ciocca, Stuart K Calderwood
May 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stefan StanglGabriele Multhoff
Feb 6, 2008·Journal of Neuro-oncology·G MinnitiR Maurizi Enrici
Jul 22, 2008·Current Opinion in Cell Biology·Konrad Krzewski, Jack L Strominger
Apr 24, 2010·Nature Reviews. Cancer·Jason T Huse, Eric C Holland
Aug 9, 2012·Journal of Visualized Experiments : JoVE·Gregory J GageWilliam Shain
Oct 24, 2014·Oncoimmunology·Hans Klingemann
May 7, 2015·Pharmacology & Therapeutics·Constantinos Alifieris, Dimitrios T Trafalis
Jul 23, 2015·Radiation Oncology·Naoya MurakamiGabriele Multhoff
Jul 29, 2015·Brain, Behavior, and Immunity·Patrícia DominguesMaría Dolores Tabernero
Sep 13, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erik AmesWilliam J Murphy
Feb 16, 2016·Expert Opinion on Therapeutic Targets·Laura Garros-RegulezAnder Matheu
Feb 24, 2016·Cancer Letters·Sanjay KumarManoj Mishra
Mar 15, 2016·JCI Insight·Konrad GabrusiewiczAmy B Heimberger
Jun 14, 2016·Human Vaccines & Immunotherapeutics·Irina V Guzhova, Boris A Margulis
Aug 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Tsuyoshi KiniwaAtsushi Miyajima
Sep 25, 2016·Neuro-oncology·Andreas F HottingerRoger Stupp
May 14, 2017·Molecular Oncology·Thatchawan ThanasupawatSabine Hombach-Klonisch
Aug 23, 2017·Journal of Visualized Experiments : JoVE·Fadi KandarianMaura Rossetti
Nov 23, 2017·Cells·Ana Rita MonteiroPatrícia A Madureira
Nov 23, 2017·Immunity·Aharon G FreudMichael A Caligiuri
Jun 6, 2018·Frontiers in Immunology·Zhihong Chen, Dolores Hambardzumyan
Sep 14, 2018·Nature Reviews. Immunology·Laura ChiossoneEric Vivier
Oct 29, 2018·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Shahla ShojaeiSaeid Ghavami
Jan 10, 2019·Nature·Neeha Zaidi, Elizabeth M Jaffee
Jan 15, 2019·Multiple Sclerosis and Related Disorders·Sahar FarhangiMohammad Javan
Jan 29, 2019·Frontiers in Pharmacology·Ruo Qiao ChenXiao Qian Chen
Jan 30, 2019·Journal of Cellular Physiology·Qing GuoAn-Hua Wu
Feb 16, 2019·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Leila PirmoradiShahla Shojaei
Mar 8, 2019·Nature Medicine·Hirotaka ItoE Antonio Chiocca
Apr 12, 2019·European Journal of Pharmacology·Bahram MiraniMohsen Akbari
May 11, 2019·Nature Communications·Nidhi Kedia-Mehta, David K Finlay
May 30, 2019·Clinical & Translational Immunology·Michael P BrownTessa Gargett

Methods Mentioned

flow cytometry
confocal microscopy
density gradient centrifugation

Related Concepts

Blood - Brain Barrier Anatomy
Natural Killer Cells
Magnetic Resonance Imaging
CD57 Antigens
Cytotoxicity Assay
Heat-Shock Proteins 70
Cell Therapy
Tumor Site

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.