학술논문
Radiation combined with oncolytic vaccinia virus provides pronounced antitumor efficacy and induces immune protection in an aggressive glioblastoma model.
Document Type
Academic Journal
Author
Storozynsky QT; Department of Oncology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB, Canada.; Agopsowicz KC; Department of Oncology, University of Alberta, Edmonton, AB, Canada.; Noyce RS; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.; Bukhari AB; Department of Oncology, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB, Canada.; Han X; Department of Oncology, University of Alberta, Edmonton, AB, Canada; Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.; Snyder N; Department of Oncology, University of Alberta, Edmonton, AB, Canada.; Umer BA; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.; Gamper AM; Department of Oncology, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB, Canada.; Godbout R; Department of Oncology, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB, Canada.; Evans DH; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada.; Hitt MM; Department of Oncology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta (CRINA), University of Alberta, Edmonton, AB, Canada. Electronic address: mhitt@ualberta.ca.
Source
Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE
Subject
Language
English
Abstract
Glioblastoma (GB) is a malignant and immune-suppressed brain cancer that remains incurable despite the current standard of care. Radiotherapy is a mainstay of GB treatment, however invasive cancer cells outside the irradiated field and radioresistance preclude complete eradication of GB cells. Oncolytic virus therapy harnesses tumor-selective viruses to spread through and destroy tumors while stimulating antitumor immune responses, and thus has potential for use following radiotherapy. We demonstrate that oncolytic ΔF4LΔJ2R vaccinia virus (VACV) replicates in and induces cytotoxicity of irradiated brain tumor initiating cells in vitro. Importantly, a single 10 Gy dose of radiation combined with ΔF4LΔJ2R VACV produced considerably superior anticancer effects relative to either monotherapy when treating immune-competent orthotopic CT2A-luc mouse models-significantly extending survival and curing the majority of mice. Mice cured by the combination displayed significantly increased survival relative to naïve age-matched controls following intracranial tumor challenge, with some complete rejections. Further, the combination therapy was associated with an increased ratio of CD8 + effector T cells to regulatory T cells compared to either monotherapy. This study validates the use of radiation with an oncolytic ΔF4LΔJ2R VACV to improve treatment of this malignant brain cancer.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Evans has been awarded U.S. and other patents as a co-inventor of related oncolytic virus technologies. Other authors declare they have no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Evans has been awarded U.S. and other patents as a co-inventor of related oncolytic virus technologies. Other authors declare they have no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)