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Determinants for Effective ALECSAT Immunotherapy Treatment on Autologous Patient-Derived Glioblastoma Stem Cells.

Journal article
Authors Anna Wenger
Katja Werlenius
Alexander Hallner
Fredrik Bergh Thorén
Dan Farahmand
Magnus Tisell
Anja Smits
Bertil Rydenhag
Asgeir Store Jakola
Helena Carén
Published in Neoplasia
Volume 20
Issue 1
Pages 25-31
ISSN 1476-5586
Publication year 2018
Published at Institute of Clinical Sciences, Department of Oncology
Sahlgrenska Cancer Center
Institute of Biomedicine, Department of Pathology
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Pages 25-31
Language en
Links dx.doi.org/10.1016/j.neo.2017.10.00...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cancer and Oncology, Cell and Molecular Biology

Abstract

Glioblastoma (GBM) is the most aggressive primary brain tumor with a median survival of less than 15 months, emphasizing the need for better treatments. Immunotherapy as a treatment for improving or aiding the patient's own immune defense to target the tumor has been suggested for GBM. A randomized clinical trial of adoptive cell transfer using ALECSAT (Autologous Lymphoid Effector Cells Specific Against Tumor Cells) is currently ongoing in Sweden. Here we performed a paired pre-clinical study to investigate the composition and in vitro effect of ALECSAT and identify determinants for the effect using autologous GBM-derived cancer stem cells (CSC), immunocytochemistry and flow cytometry. We show a clear dose-response relationship of ALECSAT on CSC, suggesting that the number of infused cells is of importance. In addition, the in vitro effect of ALECSAT on CSC correlated significantly to the blood count of T helper (Th) cells in the patient indicating a potential benefit of collecting cells for ALECSAT preparation at an even earlier stage when patients generally have a better blood count. The factors identified in this study will be important to consider in the design of future immunotherapy trials to achieve prolonged survival.

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