Judith Proske1, Lisa Walter2, Elisabeth Bumes1, Markus Hutterer1, Arabel Vollmann-Zwerenz1, Ilker Y Eyüpoglu3, Nicolai E Savaskan3, Corinna Seliger1, Peter Hau1, Martin Uhl4. 1. Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University of Regensburg Medical School, Regensburg, Germany. 2. Department of Dermatology, University Hospital, University of Erlangen-Nürnberg, Erlangen, Germany. 3. Department of Neurosurgery, University Hospital, University of Erlangen-Nürnberg, Erlangen, Germany. 4. Department of Neurology, University Hospital, University of Erlangen-Nürnberg, Erlangen, Germany martin.uhl@uk-erlangen.de.
Abstract
BACKGROUND/AIM: The combination of radiotherapy, temozolomide and valproic acid (VPA) has shown some promise in retrospective analyses of patients with glioblastoma, although their mechanisms of action remain unknown. MATERIALS AND METHODS: We investigated the in vitro and in vivo effects of pretreating glioma cells with temozolomide and VPA as an immunization strategy to boost an adaptive immune response in a syngeneic mouse model. RESULTS: Temozolomide and VPA induced autophagy in GL261 glioma cells, and caused tumor antigen-specific T-cells to become activated effector T-cells. Mice with a pre-existing glioma showed no improvement in clinical outcome when immunized with temozolomide- and VPA-treated glioma cells. CONCLUSION: Although temozolomide and VPA treatment of glioma cells can boost the adaptive immune response, in the context of a vaccine therapy, additional factors are necessary to eradicate the tumor and improve survival. Copyright
BACKGROUND/AIM: The combination of radiotherapy, temozolomide and valproic acid (VPA) has shown some promise in retrospective analyses of patients with glioblastoma, although their mechanisms of action remain unknown. MATERIALS AND METHODS: We investigated the in vitro and in vivo effects of pretreating glioma cells with temozolomide and VPA as an immunization strategy to boost an adaptive immune response in a syngeneic mouse model. RESULTS:Temozolomide and VPA induced autophagy in GL261 glioma cells, and caused tumor antigen-specific T-cells to become activated effector T-cells. Mice with a pre-existing glioma showed no improvement in clinical outcome when immunized with temozolomide- and VPA-treated glioma cells. CONCLUSION: Although temozolomide and VPA treatment of glioma cells can boost the adaptive immune response, in the context of a vaccine therapy, additional factors are necessary to eradicate the tumor and improve survival. Copyright
Authors: Shamini Murugavel; Antoinette Bugyei-Twum; Pratiek N Matkar; Husain Al-Mubarak; Hao H Chen; Mohamed Adam; Shubha Jain; Tanya Narang; Rawand M Abdin; Mohammad Qadura; Kim A Connelly; Howard Leong-Poi; Krishna K Singh Journal: Front Pharmacol Date: 2018-07-11 Impact factor: 5.810