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John D.
Christie and E.
of Brigham and Women's Hospital, Harvard Medical School, Massachusetts, USA.
Antonio Chiocca published an article in the journal Nature Medicine in August 2022, introducing the results
of the clinical trial of Todo et al.
using oncolytic viruses to treat recurrent glioblastoma.
—Excerpted from the article chapter
【Ref: Christie JD & Chiocca EA.
Nat Med.
2022 Aug; 28(8):1540-1542.
doi: 10.
1038/s41591-022-01901-4.
】
Research background
Glioblastoma (GBM) is a highly aggressive brain tumor with a 5-year survival rate of less than 10% and is highly prone to recurrence
.
Clinical trials have shown that existing treatments do not improve survival in
patients with recurrent glioblastoma.
John D.
Christie and E.
of Brigham and Women's Hospital, Harvard Medical School, Massachusetts, USA.
Antonio Chiocca published an article in the journal Nature Medicine in August 2022, introducing the results
of the clinical trial of Todo et al.
using oncolytic viruses to treat recurrent glioblastoma.
Research methods
injected oncolytic herpes simplex virus G4∆7 into the tumor tissues
of 19 patients with recurrent GBM (rGBM) by stereotactic method.
The 1-year survival rate of patients is 84%, which is much higher than the 15% expected survival rate of 1 year; The median overall survival (mOS) of patients with the first G47∆ injection was 20.
2 months, indicating significant progress
in the treatment of rGBM.
Research results
The study still has limitations; The sample size is small and there is considerable biological heterogeneity
.
For example, 6 of the 19 patients had IDH gene mutations, and the methylation data of MGMT promoter were not uniform
.
Three of the 19 patients survived for more than 3 years after treatment, indicating that there is indeed a clinical benefit
of this treatment.
While previous trials of oncolytic viral therapy have used a single stereotactic injection, the G47 ∆ was injected up to 6 times over a five-month period, combined with tumor biopsy
.
Studies have shown that patients are fairly well
tolerated with repeated dosing and biopsies.
At the same time, it breaks through the limitations
of the previous continuous examination of tumors.
Oncolytic viruses exert their antitumor effects through selective infection, replication, and biodistribution in tumors, causing cytotoxicity and immunogenic cell death, leading to an increase in the host's innate inflammatory response, thereby generating a tumor microenvironment
conducive to adaptive T cell-mediated antitumor immune responses.
The results of tumor biopsy performed by Todo et al.
showed that repeated administration can lead to an increase in invasive CD4+ and CD8+ T cells and a decrease
in FOXP3+ cells.
However, despite repeated injections, the authors did not see evidence of G47 ∆ persistence within tumors, nor were they able to study the induced alterations
of G47 ∆ in the cellular and molecular tumor microenvironment.
Conclusion of the study
The researchers observed that after a series of treatments, rGBM was infiltrated by an increasing number of effector T cells, providing a pathway for the immune "cold" GBM microenvironment to transform into a "hot" GBM microenvironment so that the immune system can more easily recognize and eliminate
it.
