Millions of viruses have been injected into the brain, and the survival period of children with fatal tumors has more than doubled!

▎The editing doctors of WuXi AppTec's content team inject millions of copies of the virus directly into the children's brains to infect their tumors and stimulate the immune system to attack.

Under this "unusual" treatment, the life expectancy of more than a dozen children has reached more than twice that of the past patients! This is not a bizarre science fiction plot, but the result of a blockbuster clinical trial for brain tumors in children.

The data of this study will be announced at the 2021 annual meeting of the American Association for Cancer Research (AACR) and simultaneously published in the New England Journal of Medicine (NEJM).

Screenshot source: The New England Journal of Medicine Glioma is a fatal childhood tumor that has been lacking effective treatment.

For 30 years, the survival rate of these children has not improved.

Nowadays, this emerging "oncolytic virus" has made important progress, which is expected to open a new perspective for treatment.

"This is the first step and also a critical step.

" said the research leader, Dr.
Gregory Friedman, a childhood cancer expert at the University of Alabama.

Dr.
Howard Kaufman, director of the Oncolytic Virus Research Laboratory at Massachusetts General Hospital (MGH), who did not participate in the trial, commented that although the number of patients in the study was small, the data from this early trial looked promising.

"This is a terrible disease, and there is almost no response to any treatment.

Therefore, the observation of some beneficial signs and quite tolerable safety in this trial is a very important discovery.

" Image source: 123RF through pathogens The idea of ​​stimulating the body's immune response to treat cancer and other diseases has been around for a long time and has been confirmed in some experiments.

A typical example is that BCG replaced surgical resection in the 1980s and became the first choice for the treatment of early in situ bladder cancer.

"Oncolytic viruses" also follow this concept.
By infecting tumors, not only can they directly kill cells, but they can also activate the body's immune response to tumors.

They have shown positive effects in the treatment of melanoma, head and neck cancer and other cancer types.

This phase 1 trial explored the application of oncolytic viruses in children with high-grade gliomas.

High-grade gliomas account for 8% to 10% of brain tumors in children.

Among newly diagnosed children receiving standard radiotherapy and chemotherapy, the 3-year event-free survival rate is only 11% to 22%.

Moreover, this disease is prone to recurrence.
Once it recurs, the average survival time is only 5.
6 months.

For a small number of children who have cured high-grade gliomas, conventional therapies may also irreversibly damage brain development.

Due to challenges such as low somatic mutation burden, inter-tumor and intra-tumor heterogeneity, mostly immune silence or "cold" tumors, and blood-brain barrier limiting drug delivery, the development of new therapies for high-grade gliomas in children is full of challenges.

Oncolytic viruses can be directly inoculated into tumors to avoid the blood-brain barrier and preferentially infect nerve tissue.
These characteristics make it an ideal choice for the treatment of brain tumors.

In pre-clinical studies, researchers found that children’s brain tumors are highly sensitive to the following oncolytic virus therapies: genetically engineered herpes simplex virus type 1 (HSV-1) G207, HSV-1 lacks necessary for replication in normal brain tissue Therefore, this prevents HSV-1 from infecting normal cells and only infects cancer cells.

Image source: 123RF In this trial, 12 patients with high-grade glioma aged 7-18 years received G207 treatment.

The trial included children and adolescents with recurrent or progressive supratentorial brain tumors, divided into 4 dose cohorts.

The patient first needs to receive stereotactic therapy, with a maximum of 4 intratumoral catheters inserted.

Patients receive G207 administration (107 or 108 plaque forming units) on the second day, and the researcher will control the input rate to ensure that the administration lasts for 6 hours.

Within 24 hours after G207 administration, half of the patients (cohorts 3 and 4) also received gross tumor volume radiotherapy (5 Gy).

Radiotherapy helps the virus spread and infect more cancer cells.

The results show that the safety of G207 treatment is acceptable.

After the investigator's assessment, no dose-limiting toxic effects or serious adverse events were attributed to G207, which was included in the maximum dose group (108 plaque forming units + 5 Gy radiotherapy).

There are 20 cases of grade 1 adverse events that may be related to G207.

Complications and minor side effects associated with surgery include nausea, vomiting, diarrhea, and fatigue.

In addition, no virus shedding was detected.

What's more gratifying is that the research team observed evidence that G207 brings relief to patients.

Imaging, neuropathology, or clinical remission was observed in 11 patients.

The median overall survival of these patients was 12.
2 months (95% confidence interval 8.
0-16.
4).

As of June 5, 2020, after receiving G207 treatment for 18 months, 4 out of 11 patients are still alive.

This has been 1-2 times longer than the survival period of the existing conventional treatment! ▲After a child is treated (right), the activated immune cells (brown) in the brain tumor increase.

(Image source: University of Alabama) In addition, 4 patients underwent biopsy.
The results showed that G207 also transformed immune "cold" tumors into "hot" tumors, significantly increasing the number of tumor-infiltrating lymphocytes.

This shows that under the effect of this therapy, the immune system is better attacking cancer cells.

The research team also observed that the presence of HSV-1 antibodies in the body before treatment may affect the survival benefits of patients.

The median overall survival of patients with changes in serum antibodies after exposure to HSV-1 was 18.
3 months, while the median survival of the three patients with anti-HSV-1 IgG antibodies before the study was only 5.
1 months.

Fortunately, although 70%-90% of adults have HSV-1 antibodies, most children are seronegative.

Image source: 123RFJake Kestler was one of the subjects who received treatment when he was 12 years old.

Although he left the world 16 months later, his father, Mr.
Josh Kestler, said, “We will never regret trying this kind of treatment.

He lived for one year and four months, and he has enough time to celebrate his experience.
Commandment (
the coming-of-age ceremony for Jewish boys).
I went to Hawaii with my family and witnessed the birth of a younger brother.
" The Kestler family who benefited from the treatment also founded the Trail Blazers for Kids.
Promote follow-up research.

At present, the multi-institution phase 2 clinical trial of G207 for the treatment of children with high-grade glioma is also about to start.

It is hoped that these encouraging efficacy and safety results can be verified in later clinical studies and bring new hope for survival to these children.

Related reading The new coronavirus infection made his tumor disappear! What does this mean for cancer treatment? References[1] Gregory K.
Friedman, et al.
, (2021).
Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas.
The N Engl J Med, DOI: 10.
1056/NEJMoa2024947[2] Unusual treatment shows promise for kids with brain tumors.
Retrieved April 13, 2021, from https://medicalxpress.
com/news/2021-04-unusual-treatment-kids-brain-tumors.
html[3] Deadly Brain Tumor: Survival Extended by Oncolytic Virus Product .
Retrieved April 13, 2021, from Note: This article aims to introduce the progress of medical and health research, not a treatment plan recommendation.

If you need guidance on treatment plans, please go to a regular hospital for treatment.