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Hitting the nail on the head: combining oncolytic adenovirus-mediated virotherapy and immunomodulation for the treatment of glioma

Wojciech K. Panek, J. Robert Kane, Jacob S. Young, Aida Rashidi, Julius W. Kim, Deepak Kanojia and Maciej S. Lesniak _

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Oncotarget. 2017; 8:89391-89405. https://doi.org/10.18632/oncotarget.20810

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Abstract

Wojciech K. Panek1, J. Robert Kane1, Jacob S. Young2, Aida Rashidi1, Julius W. Kim1, Deepak Kanojia1 and Maciej S. Lesniak1

1Department of Neurological Surgery, Northwestern University, Chicago, IL, 60611, USA

2Pritzker School of Medicine, University of Chicago, Chicago, IL, 60637, USA

Correspondence to:

Maciej S. Lesniak, email: maciej.lesniak@northwestern.edu

Keywords: combinatory therapy, glioma, immunomodulator(s), checkpoint blockade, oncolytic adenovirus

Received: July 15, 2017     Accepted: August 26, 2017     Published: September 11, 2017

ABSTRACT

Glioblastoma is a highly aggressive malignant brain tumor with a poor prognosis and the median survival 14.6 months. Immunomodulatory proteins and oncolytic viruses represent two treatment approaches that have recently been developed for patients with glioblastoma that could extend patient survival and result in better treatment outcomes for patients with this disease. Together, these approaches could potentially augment the treatment efficacy and strength of these anti-tumor therapies. In addition to oncolytic activities, this combinatory approach introduces immunomodulation locally only where cancerous cells are present. This thereby results in the change of the tumor microenvironment from immune-suppressive to immune-vulnerable via activation of cytotoxic T cells or through the removal of glioma cells immune-suppressive capability. This review discusses the strengths and weaknesses of adenoviral oncolytic therapy, and highlights the genetic modifications that result in more effective and targeted viral agents. Additionally, the mechanism of action of immune-activating agents is described and the results of previous clinical trials utilizing these treatments in other solid tumors are reviewed. The feasibility, synergy, and limitations for treatments that combine these two approaches are outlined and areas for which more work is needed are considered.


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