Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study.
Clin Cancer Res
; 28(3): 498-506, 2022 02 01.
Article
em En
| MEDLINE
| ID: mdl-35105718
ABSTRACT
PURPOSE:
Previously, clinical trials of experimental virotherapy for recurrent glioblastoma multiforme (GBM) demonstrated that inoculation with a conditionally replication-competent Δγ134.5 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. PATIENTS ANDMETHODS:
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.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.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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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RNA Neoplásico
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Ensaios Clínicos Fase I como Assunto
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Simplexvirus
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Glioblastoma
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Perfilação da Expressão Gênica
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Vírus Oncolíticos
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Terapia Viral Oncolítica
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Recidiva Local de Neoplasia
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2022
Tipo de documento:
Article