Disclaimer — This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University
of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on
publicly available information and may not be provide complete analyses of all relevant data. If this paper is used for any
purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at
the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk.
GENETICALLY RE-ENGINEERED POLIOVIRUS FOR TREATMENT OF
GLIOBLASTOMA
Kelsey Toplak, kat103@pitt.edu, Mohboobin 6:00, Patrick Siembida, pds21@pitt.edu, Sanchez 10:00
Revised Proposal -- For nearly 100 years, researchers have
been investigating the use of various viruses to treat several
types of cancer. And for the last 25 years, Dr. Matthias
Gromeier, associate professor of surgery and molecular
genetics and microbiology at Duke University has been
delving into the effects of a re-engineered poliovirus on a
form of brain cancer known as glioblastoma [1]. The
genetically engineered poliovirus, created by replacing a
genetic element with a new element that allows for the new
virus to attack tumor cells while avoiding healthy tissue,
known as PVS-RIPO, has shown promising signs of success
in treating glioblastoma, offering hope of survival to persons
suffering from this extremely fatal cancer and the potential to
advance research in the field of virotherapy.
Poliovirus is a deadly pathogen that leads to the
development of poliomyelitis, more commonly known as
polio. Poliovirus was once the cause of a global
pandemic. However, through the power of modern medicine
and genetic engineering the virus has developed a new
application in the treatment of glioblastoma. In order for the
poliovirus to work against cancers in patients the virus must
target cancer cells and kill them while leaving healthy cells
unharmed. Additionally, the virus must not cause disease in
the patient. Due to this safety concern, before treatment, the
genetic code that causes poliomyelitis is removed and is
replaced by a piece of genetic code from the cold-causing
rhinovirus [1]. Specifically, the IRES element of the
poliovirus vaccine is removed and then replaced by the
human rhinovirus type 2[1]. Also, the poliovirus leaves
normal, healthy cells unharmed because its ability to kill and
grow relies on biochemical abnormalities present exclusively
in cancer cells. When treatment begins, the virus is delivered
directly to the tumor where it then infects and kills tumor cells.
Currently the virus is in phase I of clinical trials but the
results thus far look promising. As of March 2015, 16% of
patients in the trial saw their tumors shrink for six months.
Currently, in trials, the poliovirus is only being used to
treat glioblastoma. Despite this fact, there is reason to
assume that the virus could be used to alleviate other forms
of cancer. Cancer treatment is a major point of emphasis in
today’s medical society as hundreds of thousands of people
are killed by the disease every year [2].
Success with this trial, has the potential to create new
methodologies and breakthroughs with other vaccines and
diseases, as well as help to the general population.
Bioengineers, and more specifically biomedical
engineers, according to the Biomedical Engineering Society
Code of Ethics must “Use their knowledge, skills, and
abilities to enhance the safety, health, and welfare of the
public” [3]. It is with that interest in mind that this poliovirus
technology is extraordinarily important. Presently, there is
debate about whether the engineered poliovirus will make it
to market, even if it is approved by the FDA due to a
potentially flawed business plan [2]. As a onetime use drug,
it may not be able to make a profit, which would mean it could
not make it to market and those fatally suffering from
glioblastoma would not receive treatment.
PVS-RIPO is a very new breakthrough in clinical trials as
a form of treatment for cancers. As such, there exists great
deal of academic journals, articles, and lectures covering
genetic engineering of viruses accessible through various
databases, such as Academic Search Premier, and the web.
As for the PVS-RIPO virus, its creator, Dr. Gromeier has
published some of his findings leading up to the clinical trials,
which will be used in the research of this paper as well. As
research on the poliovirus is ongoing, Dr. Gromeier still
resides at Duke and is a potential source via email.
Additionally, the PVS-RIPO virus and the potential cure for
glioblastoma took the media by storm. Several newspapers,
magazines, and other media outlets will serve as sources for
data on the public opinion and general background on PVSRIPO. Organizationally, we plan to research the general
history of the use of viruses to treat diseases, followed by a
detailed analysis of the polio virus and glioblastoma.
Additionally, in depth research will be conducted on genetic
engineering as a field and with respect to how genetic
engineering can be used to manipulate viruses. With these
topics introduced we will proceed to relate them to each other
with respect to Dr. Gromeier’s work and PVS-RIPO
specifically. The majority of our research will center on PVSRIPO and its creation, clinical trials, potential to go to
market, and the impact it could make on society.
REFERENCES
University of Pittsburgh Swanson School of Engineering
2016/01/29
1
Kelsey Toplak
Patrick Siembida
[1]. M. Gromeier.“A Current Phase I Trial for Recurrent
Glioblastoma Patients Opens for Accrual at the Preston
Robert Tisch Brain Tumor Center.” Duke University Medical
Center. (Online article)
http://www.cancer.duke.edu/btc/modules/research3/index.ph
p?id=41
[2]. A. Weintraub. (30 March, 2015). “Here’s What ‘60
Minutes’ Didn’t Tell You About the ‘Miracle’ Glioblastoma
Treatment.” Forbes. (Online Article).
http://www.forbes.com/sites/arleneweintraub/2015/03/30/her
es-what-60-minutes-didnt-tell-you-about-the-miracleglioblastoma-treatment/#2715e4857a0b21a7bd29719
[3]. (February 2004) “Code of Ethics.” Biomedical
Engineering
Society.
(Code
of
ethics).
http://bmes.org/files/2004%20Approved%20%20Code%20o
f%20Ethics(2).pdf
will also provide us with certain statistics that will be useful
in our paper.
C. Goetz, M. Gromeier. (17 March 2010). “Preparing an
oncolytic poliovirus recombinant for clinical application
against glioblastoma multiforme.” Cytokine & Growth Factor
Reviews.
(Online
Academic
Journal).
DOI:
10.1016/j.cytojfr.2010.02.005. pp.197-203.
http://web.b.ebscohost.com/ehost/command/detail?sid=670b
ac2c-3728-4aaf-bed078613d6cbe32%40sessionmgr111&vid=4&hid=124
In Cytokine and Growth Factor Reviews, Dr.
Gromeier’s work on the PVS-RIPO virus can be found. His
paper explains his current research on the virus in great detail
as well as where his research will lead as the virus heads to
clinical trials. As such, this source will be invaluable to
understanding and conveying the current research being done
on the polio virus and glioblastoma.
ANNOTATED BIBLIOGRAPHY
M. Gromeier.“A Current Phase I Trial for Recurrent
Glioblastoma Patients Opens for Accrual at the Preston
Robert Tisch Brain Tumor Center.” Duke University Medical
Center. (Online article)
http://www.cancer.duke.edu/btc/modules/research3/index.ph
p?id=41
This online article, lists the details of the phase 1 clinical
trial for recurrent glioblastoma patients. The article describes
the background of the poliovirus being used to treat
glioblastoma. Also, the article discusses how the virus works,
the plans for the future, the clinical trials, and the greater
significance of the virus. Information from this article will
help us to provide a basic overview to introduce readers to the
poliovirus.
M. Boudin, A. Dennis. (2014, May 5). “Killing Cancer with
Polio.”
People.
(Online
article).
pp.
174-178.
http://web.b.ebscohost.com/ehost/detail/detail?sid=12f2e36a
-2c90-4567-a5e45d7195796404%40sessionmgr198&vid=8&hid=105&bdata
=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#anchor=AN00957
47947-4&AN=95747947&db=aph
The periodical from People magazine gives a personalized
description of one woman’s experience with glioblastoma and
the poliovirus trial. The article describes in detail how the
procedure was conducted as the poliovirus was injected
directly into the tumor. The information from the periodical
will help us to provide a detailed description of one’s personal
experience with glioblastoma and an accurate description of
the procedure.
N. Nelson. (1999) “Viruses and Cancer.” Journal of the
National Cancer Institute. DOI:10.1093/jnci/91.20.1709.
(Academic Journal)
This journal article comes from the Journal of the National
Cancer Institute. It specifically discusses the history of the use
of viruses in attempt to treat forms of cancer. The polio virus
is mentioned specifically. Nelson points out that at the time
the polio virus would eliminate part of the tumor, but the
patient’s immuno response would override any affect of the
virus in a short period of time. As such, this source will serve
as a comparison between prior attempts of treating cancer
with polio virus, and Dr. Gromeier’s PVS-RIPO strain.
(February 2004) “Code of Ethics.” Biomedical Engineering
Society. (Code of ethics).
The Biomedical Engineering Society, often referred to as
BMES, is a respected national professional society for those
in the bioengineering field. As such, bioengineers must follow
the code of ethics set forth by the BMES. The code of ethics
will be used to understand and explain why poliovirus
bioengineering researchers are working on this topic and the
clinical trial process.
“Glioblastoma (GBM).” American Brain Tumor Association.
(Online
Article).
http://www.abta.org/brain-tumorinformation/types-oftumors/glioblastoma.html?referrer=https://www.google.com/
This online article, from the American Brain Tumor
Association gives a detailed description of glioblastoma. It
describes many aspects of the disease including symptoms,
incidence, treatment and prognosis. This will provide us with
helpful background that will allow us to accurately introduce
the disease to our readers. The information from the article
D. Sze, T. Reid, S. Rose. (August 2013). “Oncolytic
Virotherapy.” Journal of Vascular and Interventional
Radiology. DOI:10.1016/j.vir.2013.05.040. pp. 11151122.(Academic Journal).
This source is found in the Journal of Vascular and
Interventional Radiology on the topic on oncolytic viruses.
This article details a history of oncolytic viruses as well as
some of the research conducted with them in the past. This
will prove useful in explaining the origins of the PVS-RIPO
2
Kelsey Toplak
Patrick Siembida
virus and the rationale behind using a virus as a form of cancer
treatment.
A. Weintraub. (30 March, 2015). “Here’s What ‘60 Minutes’
Didn’t Tell You About the ‘Miracle’ Glioblastoma
Treatment.” Forbes. (Online Article).
http://www.forbes.com/sites/arleneweintraub/2015/03/30/her
es-what-60-minutes-didnt-tell-you-about-the-miracleglioblastoma-treatment/#2715e4857a0b21a7bd29719a
The online article, from a popular press article details
some of the possible shortcomings of the treatment.
Additionally, the article describes how other viruses have
been used to treat various forms of cancer. Information from
the article will assist us in our description of the poliovirus by
providing us with the problems that the virus needs to
overcome and will supply us with helpful background info on
cancer treating viruses.
3