Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma

Abstract

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the “immune-cold” nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

Case Report: Low-grade glioma with NF1 loss of function mimicking diffuse intrinsic pontine glioma

“…However, this case is emblematic because of the marked impact the tissue diagnosis has had on this patient's prognosis and management. Notably, other recent studies have also demonstrated that molecular information obtained from biopsies can guide potential treatment options, including the use of targeted inhibitors ( 12 – 15 ). Nonetheless, given the potential for complications and the incredible heterogeneity in the presentation of pontine glioneuronal masses, we suggest that the decision on whether to perform a biopsy should be based on the clinical judgment of risk and benefit by the surgeon and neuro-oncologist as well as shared decision-making with the patient.…”

Recurrent Glioblastoma—Molecular Underpinnings and Evolving Treatment Paradigms

“…OV combination therapy is of increasing research interest [ 187 ]. Nassiri et al [ 147 ] tested a combination therapy of the oncolytic adenovirus DNX-2401 with a checkpoint inhibitor in a cohort of 49 patients with recurrent glioblastoma.…”