Living Virus Promises
Novel Approach to
Killing Cancer Cells
By Francis Giles, MD and Monica Mita, MD
Qualifying sarcoma patients at
the Cancer Therapy & Research
Center are among the nation’s
first to enter a new Phase II
clinical study for a novel therapy that
uses a living virus to kill cancer cells.
Reolysin® is not a chemotherapy
drug, but living virus belonging to the
reoviridae family. The reovirus is one
of three viruses from the reoviridae
family can infect humans – the other
two are the orbivirus and the rotavirus – but the reovirus appears to produce
the least pathology. Found throughout
the world, reoviruses can create mild
infections in humans that are limited
to the upper respiratory and gastrointestinal
tracts. In normal, healthy
cells, the reovirus can’t reproduce
because an enzyme named PKR (double
stranded RNA-activated protein
kinase) is present and active.
The PKR enzyme is responsible for
virus inactivation through inhibition
of viral protein synthesis in normal
cells. In cancer cells this enzyme is
inactivated and as a result, the virus
can replicate in cancer cells and eventually
result in oncolysis. Preclinical
studies with Reolysin show that the
virus replicates specifically in and is
cytopatic to transformed or malignant
cells, specifically those with an activated
Ras signaling pathway.
In previous phase I studies, the
main side-effects associated with the
Reolysin infusion were fever, headache,
flu-like syndrome, chills, fatigue, rhinorrhea,
cough, myalgia, sweating and
mild and transient hematological toxicity.
Gastrointestinal symptoms like
nausea, vomiting and diarrhea also
have occurred occasionally.
Reolysin demonstrated success
against tumors during earlier phases of
preclinical and clinical testing. Phase I
studies showed evidence of antitumor
activity in patients with prostate, colorectal,
head and neck and esophageal
cancer.
The CTRC Institute first began Phase
II studies with the reovirus in July
2007 in conjunction with Oncolytics
Biotech, Inc., a biotechnology company.
The current study (REO-014) is an
open-label, single agent study with the
primary objectives of measuring tumor
responses and duration of response,
and describing the antitumor activity.
Eligible patients are those who have
a bone or soft tissue sarcoma that has
spread to the lung and who are
deemed by their physicians to be unresponsive
to or untreatable by standard
therapies. These include patients with
osteosarcoma, Ewing sarcoma family
tumors, malignant fibrous histiocytoma,
synovial sarcoma, bribrosarcoma
and leiomyosarcoma.
Reolysin is administered intravenously
daily for five days every 28
days. If well tolerated and in the absence
of progression, patients may
receive additional five-day therapy
cycles every four weeks for a maximum
of eight cycles. Up to 52 patients will
be enrolled.
This article was co-authored
by the director of the
CTRC Institute for Drug
Development, Francis
Giles, MD, a researcher
and clinical scientist specializing
in leukemia, lymphoma
and multiple myeloma,
and Monica Mita,
MD, a medical oncologist
and principal investigator
at the CTRC Institute
for Drug Development
specializing in sarcoma
and breast cancer.
back to top
