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Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Feb 01; Vol. 28 (3), pp. 498-506. - Publication Year :
- 2022
-
Abstract
- Purpose: Previously, clinical trials of experimental virotherapy for recurrent glioblastoma multiforme (GBM) demonstrated that inoculation with a conditionally replication-competent Δγ <subscript>1</subscript> 34.5 oncolytic herpes simplex virus (oHSV), G207, was safe. Following the initial safety study, a phase Ib trial enrolled 6 adult patients diagnosed with GBM recurrence from which tumor tissue was banked for future studies.<br />Patients and Methods: Here, we analyzed tumor RNA sequencing (RNA-seq) data obtained from pre- and posttreatment (collected 2 or 5 days after G207 injection) biopsies from the phase Ib study patients.<br />Results: Using a Spearman rank-order correlation analysis, we identified approximately 500 genes whose expression pattern correlated with survival duration. Many of these genes were enriched for the intrinsic IFN-mediated antiviral and adaptive immune functional responses, including immune cell chemotaxis and antigen presentation to T-cells. Furthermore, we show that the expression of several T-cell-related genes was highest in the patient with the longest survival after G207 inoculation.<br />Conclusions: Our data support that the oHSV-induced type I IFN production and the subsequent recruitment of an adaptive immune response differed between enrolled patients and showed association with survival duration in patients with recurrent malignant glioma after treatment with an early generation oHSV.<br /> (©2022 The Authors; Published by the American Association for Cancer Research.)
- Subjects :
- Adult
Aged
Brain Neoplasms immunology
Brain Neoplasms mortality
Female
Glioblastoma immunology
Glioblastoma mortality
Humans
Male
Middle Aged
Neoplasm Recurrence, Local mortality
Survival Rate
Brain Neoplasms genetics
Brain Neoplasms therapy
Clinical Trials, Phase I as Topic
Gene Expression Profiling methods
Glioblastoma genetics
Glioblastoma therapy
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local immunology
Neoplasm Recurrence, Local therapy
Oncolytic Virotherapy methods
Oncolytic Viruses
RNA, Neoplasm genetics
Simplexvirus
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 28
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 35105718
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-21-2636