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Combination of oncolytic viruses and immune checkpoint inhibitors in glioblastoma
Kunal Desai1, Anne Hubben1, Manmeet Ahluwalia2
1 Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
2 Department of Medicine, Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA
Correspondence Address:
Dr. Anne Hubben
Department of Internal Medicine, Cleveland Clinic, 9500 Euclid Avenue, Na10, Cleveland, OH 44195
USA
Dr. Kunal Desai
Department of Internal Medicine, Cleveland Clinic, 9500 Euclid Avenue, NA10, Cleveland, OH 44195
USA
Dr. Manmeet Ahluwalia
Burkhardt Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, S73, Cleveland, OH 44195
USA
 Source of Support: None, Conflict of Interest: None  | 2 |
DOI: 10.4103/glioma.glioma_5_19
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Glioblastoma is associated with poor prognosis with a mean survival of 15 months after diagnosis. The current standard of care includes surgery, radiation, and temozolomide with the use of tumor-treating fields in select patient population. The past decade has witnessed a convergence in our understanding of tumor biology and the role of the immune system in fighting cancer. The highly immunosuppressive tumor microenvironment exerted by glioblastoma cells has contributed to the lack of success of novel immunotherapies till date (including checkpoint inhibitors). Oncolytic viral-based approaches are of renewed interest given advances in tumor cell tropism, pathogenicity, and immunogenicity. More importantly, oncolytic viruses have been shown to initiate a broad immune response through various mechanisms including dual activation of the innate and adaptive arms of the host immune system. Because the initial clinical studies with monotherapy checkpoint inhibition in glioblastoma have failed to demonstrate a survival advantage, most trials in glioblastoma are testing combinations that seek to augment the immune response through mutually reinforcing approaches that can overcome the immunosuppressive milieu. Preclinical data in glioblastoma models with combined oncolytic viruses therapy and checkpoint blockade are favorable and provide rationale to initiate first-in-human trials. Even though the number of clinical trials testing this combination in glioblastoma is limited, more studies are expected in the future.
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