Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma

Wirsching, Hans-Georg; Zhang, Huajia; Szulzewsky, Frank; Arora, Sonali; Grandi, Paola; Cimino, Patrick J.; Amankulor, Nduka; Campbell, Jean S.; McFerrin, Lisa; Pattwell, Siobhan S.; Ene, Cristian; Hicks, Alexandra; Ball, Michael S.; Yan, Jing-Jou; Zhang, Jenny; Kumasaka, Debrah; Pierce, Robert H.; Weller, Michael; Finer, Mitchell; Quéva, Christophe; Houghton, A. McGarry; Holland, Eric C.

doi:10.1172/jci.insight.128217

Cited by 28 publications

(23 citation statements)

References 39 publications

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“…Beneficial combination therapy was also observed by Wirsching et al, who demonstrated that a miR-124-attenuated oHSV expressing ULBP3 promoted a localized and abscopal immune response, hence priming the TME for effective synergy with the anti-PD-1 checkpoint blockade in a GBM model [ 109 ].…”

Section: Combination Therapy In Preclinical and Clinical Settingsmentioning

confidence: 87%

Oncolytic Viruses as a Platform for the Treatment of Malignant Brain Tumors

Sostoa

Dutoit

Migliorini

2020

IJMS

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Malignant brain tumors remain incurable diseases. Although much effort has been devoted to improving patient outcome, multiple factors such as the high tumor heterogeneity, the strong tumor-induced immunosuppressive microenvironment, and the low mutational burden make the treatment of these tumors especially challenging. Thus, novel therapeutic strategies are urgent. Oncolytic viruses (OVs) are biotherapeutics that have been selected or engineered to infect and selectively kill cancer cells. Increasingly, preclinical and clinical studies demonstrate the ability of OVs to recruit T cells and induce durable immune responses against both virus and tumor, transforming a “cold” tumor microenvironment into a “hot” environment. Besides promising clinical results as a monotherapy, OVs can be powerfully combined with other cancer therapies, helping to overcome critical barriers through the creation of synergistic effects in the fight against brain cancer. Although many questions remain to be answered to fully exploit the therapeutic potential of OVs, oncolytic virotherapy will clearly be part of future treatments for patients with malignant brain tumors.

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Section: Combination Therapy In Preclinical and Clinical Settingsmentioning

confidence: 87%

Oncolytic Viruses as a Platform for the Treatment of Malignant Brain Tumors

Sostoa

Dutoit

Migliorini

2020

IJMS

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“…Mouse glioblastomas were treated with oHSV ULBP3 , an oncolytic herpes simplex virus 1 strain that was armed with a ULBP3 gene expression cassette to boost anti-cancer immunity ( Figure 1A). 5 There was a twofold increase in VEGF protein levels upon treatment with oHSV ULBP3 versus PBS in protein lysates from 5 mouse glioblastomas per group ( Figure 1B). A major proportion of VEGF is, however, immobilized in the extracellular matrix.…”

Section: Letter To the Editormentioning

confidence: 92%

“…We employed a non-immunogenic genetic model of IDH wildtype glioblastoma which is histologically, immunologically and molecularly highly similar to its human counterpart (N/tv-a;Cdkn2a -/-;Pten fl/fl :PDGF,Cre). 5 Animal research was prospectively approved by the Institutional Animal Care and Use Committee of the Fred Hutchinson Cancer Research Center, Seattle, WA (Animal assurance institutional #A3226-01; Protocol #50842). Mouse glioblastomas were treated with oHSV ULBP3 , an oncolytic herpes simplex virus 1 strain that was armed with a ULBP3 gene expression cassette to boost anti-cancer immunity ( Figure 1A).…”

Section: Letter To the Editormentioning

confidence: 99%

Cooperation of oncolytic virotherapy with VEGF-neutralizing antibody treatment in IDH wildtype glioblastoma depends on MMP9

et al. 2019

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“…For immunofluorescence stainings, formalin‐fixed paraffin‐embedded tissues were subjected to de‐paraffinization and antigen‐retrieval on the DISCOVERY XT platform (Ventana Medical Systems, Inc., Tucson) using standard protocols. Subsequently, slides were rehydrated and stained as described previously (Wirsching et al, 2019). Images were taken on a Leica DM5500B fluorescence microscope.…”

Section: Methodsmentioning

confidence: 99%

Multimodal single‐cell analysis reveals distinct radioresistant stem‐like and progenitor cell populations in murine glioma

Alexander

LaPlant

Pattwell

et al. 2020

Glia

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Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem-like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem-like properties have been used, including the fluorescence activated cell sorting (FACS)-based side population (SP) assay, which is a functional assay that enriches for stem-like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single-cell RNA sequencing of genetically-engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment.

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Arming oHSV with ULBP3 drives abscopal immunity in lymphocyte-depleted glioblastoma

Cited by 28 publications

References 39 publications

Oncolytic Viruses as a Platform for the Treatment of Malignant Brain Tumors

Oncolytic Viruses as a Platform for the Treatment of Malignant Brain Tumors

Cooperation of oncolytic virotherapy with VEGF-neutralizing antibody treatment in IDH wildtype glioblastoma depends on MMP9

Multimodal single‐cell analysis reveals distinct radioresistant stem‐like and progenitor cell populations in murine glioma

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