Clin Cancer Res 2015 Jul 31;21(14):3274-85. Epub 2015 Mar 31.
Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio.
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Cancer Res 2015 Dec 2;75(24):5273-82. Epub 2015 Dec 2.
Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio. The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Oncolytic viruses, including oncolytic herpes simplex virus (oHSV), have produced provocative therapeutic responses in patients with glioblastoma, the most aggressive brain tumor. Paradoxically, innate immune responses mediated by natural killer (NK) cells and macrophages/microglia appear to limit oHSV efficacy. Therefore, we investigated whether pretreatment with an immunosuppressive cytokine, TGFβ, might reverse these effects and thereby potentiate oHSV efficacy. Read More
Clin Cancer Res 2017 Apr 9;23(7):1809-1819. Epub 2016 Nov 9.
Department of Neurological Surgery, The Ohio State University College of Medicine, Columbus, Ohio.
Brain angiogenesis inhibitor (BAI1) facilitates phagocytosis and bacterial pathogen clearance by macrophages; however, its role in viral infections is unknown. Here, we examined the role of BAI1, and its N-terminal cleavage fragment (Vstat120) in antiviral macrophage responses to oncolytic herpes simplex virus (oHSV). Changes in infiltration and activation of monocytic and microglial cells after treatment of glioma-bearing mice brains with a control (rHSVQ1) or Vstat120-expressing (RAMBO) oHSV was analyzed using flow cytometry. Read More
Clin Cancer Res 2016 Nov 7;22(21):5265-5276. Epub 2016 Jul 7.
Department of Neurological Surgery, Dardinger Laboratory for Neuro-oncology and Neurosciences, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Purpose: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy. Read More
Int J Cancer 2017 12 26;141(11):2348-2358. Epub 2017 Aug 26.
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Read More