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Gururangan et al. Neuroimmunol Neuroinflammation 2018;5:45    Neuroimmunology and
               DOI: 10.20517/2347-8659.2018.44                                   Neuroinflammation




               Review                                                                        Open Access


               Total tumor RNA pulsed dendritic cells plus adoptive
               transfer of ex-vivo enriched autologous T-lymphocytes
               in the treatment of children with primary brain tumors


               Sridharan Gururangan, Elias Sayour, Duane A. Mitchell

               Department of Neurosurgery, Preston A. Wells Center for Brain Tumor Therapy, McKnight Brain Institute, Gainesville, FL 32608, USA.

               Correspondence to: Dr. Sridharan Gururangan, Department of Neurosurgery, Preston A. Wells Center for Brain Tumor Therapy,
               McKnight Brain Institute, Gainesville, FL 32608, USA. E-mail: gururangan@ufl.edu
               How to cite this article: Gururangan S, Sayour E, Mitchell DA. Total tumor RNA pulsed dendritic cells plus adoptive transfer of ex-vivo
               enriched autologous T-lymphocytes in the treatment of children with primary brain tumors. Neuroimmunol Neuroinflammation 2018;5:45.
               http://dx.doi.org/10.20517/2347-8659.2018.44
               Received: 31 Jul 2018     First Decision: 24 Aug 2018     Revised: 21 Sep 2018     Accepted: 15 Oct 2018     Published: 29 Oct 2018

               Science Editor: Athanassios P. Kyritsis    Copy Editor: Cui Yu    Production Editor: Zhong-Yu Guo



               Abstract
               The therapeutic approach of adoptive lymphocyte transfer (ALT) using lymphocytes primed and expanded ex-vivo
               by exposure to total tumor RNA (ttRNA) containing dendritic cells (DCs) and administered after lymphodepletive
               host conditioning in patients with refractory melanoma with brain metastases has shown excellent objective
               responses indicating that the central nervous system (CNS) is not an immune privileged site and further paved the
               way for utilization of a similar approach in other cancers. We have shown that the use of ALT + ttRNA DCs following
               either myeloablative or non-myeloablative host conditioning is feasible and safe and appears to prolong survival
               in a proportion of children with recurrent medulloblastoma who had failed standard cytotoxic therapy. Further
               refinements in this promising approach are needed to improve outcomes and extend this treatment to a broad range
               of CNS malignancies.

               Keywords: Children, brain tumors, immunotherapy, adoptive lymphocyte transfer, dendritic cell vaccine,
               lymphodepletion, total tumor RNA




               INTRODUCTION
               Primary pediatric central nervous system tumors
               Pediatric brain tumors are the commonest solid tumors in children and unfortunately the cause for the
                                                       [1]
               most cancer related mortality in this age group . Standard treatment for these patients at diagnosis includes

                           © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
                           International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
                sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
                as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
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