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

Anna Wenger; Katja Werlenius; Alexander Hallner; Fredrik Bergh Thorén; Dan Farahmand; Magnus Tisell; Anja Smits; Bertil Rydenhag; Asgeir S Jakola; Helena Carén

doi:10.1016/j.neo.2017.10.006

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

Neoplasia. 2018 Jan;20(1):25-31. doi: 10.1016/j.neo.2017.10.006. Epub 2017 Dec 1.

Authors

Affiliations

¹ Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
² Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgrenska Cancer Center, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
³ TIMM laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁶ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Neuroscience, Neurology, Uppsala University, University Hospital, Uppsala, Sweden.
⁷ Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Neurosurgery, St. Olavs University Hospital, Trondheim, Norway.
⁸ Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: helena.caren@gu.se.

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 (T_h) 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Brain Neoplasms / immunology*
Brain Neoplasms / therapy*
Cell Line, Tumor
Combined Modality Therapy
Female
Fibroblasts / metabolism
Glioblastoma / immunology*
Glioblastoma / therapy*
Humans
Immunotherapy, Adoptive / methods*
Lymphocyte Count
Male
Middle Aged
Neoplastic Stem Cells / immunology*
Radiotherapy, Adjuvant
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism