- Engineered common cold virus, Delta-24-RGD, increases
survival in recurrent glioblastoma patients.
- When Delta-24-RGD was injected into the
brain tumors, twenty
percent of recurrent glioblastoma patients lived for three years longer.
- The virus is non-toxic with minimal
side effects and by replicating within cells, they specifically target and
kill cancer cells.
Phase 1 clinical trial results show that
a common cold virus engineered to attack brain tumors increased the survival
rate in twenty percent of recurrent
The engineered virus, Delta-24-RGD, added an extra three years or more
to the overall survival time in these patients. The study was conducted by a research team
at The University of Texas MD Anderson Cancer Center and published in
the Journal of Clinical Oncology.
Glioblastoma is an
aggressive type of brain cancer that affects astrocytes, a type of cells in the
brain that supports neurons.
It is difficult to treat, and a cure is often not possible.
Treatments are aimed at slowing the progression of cancer. Recurrent
glioblastoma is when cancer strikes again after surgery and other treatments.
These patients typically have a median survival of 6 months.
The clinical trial involved 25 patients with
recurrent glioblastoma. The adenovirus called Delta-24-RGD or DNX-2401 was engineered to attack brain tumors
. The virus was injected into
the tumors of all patients to target the glioblastoma.
‘Engineered common cold virus, Delta-24-RGD, specifically targets cancer cells and triggers an immune response that kills the tumor.’
"We designed DNX-2401 to specifically
infect cancer cells, replicate inside those cells to kill them, and spread from
cell to cell in a destructive wave throughout the tumor," said senior
author and drug co-inventor Juan Fueyo, "The clinical trial shows what happens, as predicted by
our preclinical research, and it also shows that in some patients, viral
infection was followed by an immune reaction to the glioblastoma that led to
the strong responses."
The viral attack
Five of the twenty-five
or twenty percent of
recurrent glioblastoma patients lived three years longer than the expected
Three out of the five had durable complete
responses, which the research team say is exceptional for a phase 1 clinical
trial in glioblastoma.
"Many phase I trials might have one
patient who does well, so our result is unusual, but we're always cautious in
assessing results with this very difficult disease." said lead author
Frederick Lang, M.D., professor of Neurosurgery.
The toxicity associated with the treatment
was minimal, and the
dose escalation went up to the
highest concentration of the virus that could be manufactured, which indicates
that there were no dose-limiting
side effects as well.
Seventy-two percent of the
patients had some amount of tumor reduction, and the median survival among the patients was 9.5 months.
In the three patients out of the five who
achieved complete responses, brain imaging showed that there were inflammation and immune activities even a month after
treatment. This is a good sign especially since glioblastomas are normally not
recognized by the immune system
. A steady decline in the size of
the tumor was also observed.
"In the case of these long-term complete
responders, the virus breaks the tumor's shield against immune response by
killing cells, creating multiple antigen targets for the immune system,"
said co-inventor Candelaria Gomez-Manzano, M.D., associate professor of
Neuro-Oncology. "These tumors are then completely destroyed."
With no detectable tumor, minimal
initial side effects and no ongoing treatment, this method of treatment appears
to be a better alternative to other methods that come with stronger side
However, even in the three patients who had a complete response, cancer
recurred about three or four years later which ultimately became fatal. The
recurred tumor appeared as a
gliosarcoma in two cases, a tumor different from the original glioblastoma. All
three patients lived for at least 4.8 years after treatment.
- Glioblastoma - (https://www.mayoclinic.org/diseases-conditions/glioblastoma/cdc-20350148)