Conference Session (A1)
Paper 6010
THE ADENOVIRUS AND ITS APPLICATION IN VIROTHERAPY
Pegah Zarandi (ppz2@pitt.edu, 0012; Lora 6:00), Dominic Dawes (ddd28@pitt.edu, 0012; Bursic 2:00)
Abstract- As it currently stands, cancers such as leukemia
and pancreatic cancer have very low survival rates 50% and
1.1% respectively [1][2]. Conventional treatments such as
radiotherapy and chemotherapy, indiscriminately destroy
both normal and cancerous cells and can take a severe toll
on the human body. Oncolytic virotherapy is a more
progressive alternative that utilizes modified viruses that can
discern between the tumors and normally functional tissues,
while selectively terminating the mutated cells. [3]
The notion that viruses could be repurposed for
therapeutic uses is not a new concept. The effect of viral
infection on tumor cells was first observed during the 1950’s
and 1960’s when several cases of cancer remission were
reported after the patient was exposed to a virus [4]. Since
its early stages of research, the field of virotherapy has
made significant quantitative progress. In some countries,
viral therapies such as Onyx-15 and Rigvir have become
approved as viable medical treatment options for cancer
patients [3] [4]. However, there are still several factors,
such as delivery and transduction efficiency of target cells,
that need to be improved in order for virotherapy to become
a mainstream cancer treatment [5].
This paper will focus on the genetic modification of the
adenovirus H101 for use in cancer virotherapy. The paper’s
first objective will be to provide an overview of the process
of virotherapy and the science behind the modification the
H101 virus, and how it takes advantage of its specific
cellular tropism, in order to infect specific types of cancer
cells. Subsequently, we will give an overview of the biotransport and cellular biological phenomena that are
involved in the delivery of the virus, and then assess the
current issues that affect the therapy's efficacy such as, virus
delivery and transduction efficiency of target cells.
Furthermore, we will analyze various perspectives from
sources such as, scientific journals and trusted articles on
the viability and implementation of the H101 adenovirus in
oncolytic virotherapy in order to demonstrate that oncolytic
virotherapy is an applicable biotechnology. Since the ethical
and regulatory guidelines of oncolytic virotherapy can be
ambiguous, biomedical ethical handbooks will be examined
and evaluated in order to concretely delineate how oncolytic
virotherapy should be administered as a medical treatment.
University of Pittsburgh Swanson School of Engineering 1
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ANNOTATED BIBLIOGRAPHY
[6] BMES. (2004). “Biomedical Engineering Society Code
of
Ethics.”
BMES.
(Code
of
Ethics).
http://bmes.org/files/2004%20Approved%20%20Code%20o
f%20Ethics(2).pdf
The Biomedical Engineering Society created a strict
list of obligations and ethical conducts that must be upheld
by all biomedical engineers. It is made up of two biomedical
engineering professional obligations, two biomedical
engineering health care obligations, two biomedical
engineering research obligations, and two biomedical
engineering training obligations. We will include this
information within our ethics of virotherapy section in the
paper.
[1] Chen, C. Y., J. S. Senac, E. A. Weaver, S. M. May, D. F.
Jelinek, P. Greipp, T. Witzig, and M. A. Barry. "Species D
Adenoviruses as Oncolytics against B-cell Cancers."
Clinical Cancer Research 17.21 (2011): 6712-722. Web.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207036/.
This article from the National Center for
Biotechnology Information is of an experiment where 15
adenoviruses selected to represent Ad species B, C, D, E,
and F were tested in vitro against cell lines and primary
patient B cell cancers for their ability to infect, replicate in,
and kill these cells. The results showed that species D
adenoviruses have a unique ability to infect and replicate in
B cell cancers as compared to other adenovirus species. We
will use this article for statistics of survival rates of cancer
and how species D adenovirus successfully infiltrated the
cancer cells.
[5] Eager, R. M., and J. Nemunaitis. "Clinical Development
Directions in Oncolytic Viral Therapy." Cancer Gene
Therapy Cancer Gene Therapy 18.5 (2011): 305-17. Web.
http://www.nature.com/cgt/journal/v18/n5/full/cgt20117a.ht
ml.
This article from the Cancer Gene Therapy provides a
brief description of novel anticancer biologics. To date,
oncolytic virotherapy has shown to be safe, and has
generated clinical responses in tumors that are resistant to
chemotherapy or radiotherapy. In addition, the researchers
Pegah Zarandi
Dominic Dawes
wanted to maximize the efficacy of the viral therapeutics,
and to establish stable systemic delivery mechanisms. We
will use this information as evidence as to why virotherapy
is a safer and more practical option for cancer treatment.
[3] Garber, Ken. "China Approves World's First Oncolytic
Virus
Therapy
for
Cancer
Treatment."
Http://jnci.oxfordjournals.org/. Oxford University Press,
2006.
Web.
19
Jan.
2016.
http://jnci.oxfordjournals.org/content/98/5/298.full.
This article from the Journal of the National Cancer
Institute discusses how Chinese regulators approved the
world's first oncolytic viral therapy for cancer, Shanghai
Sunway Biotech's genetically modified adenovirus H101.
They expect to begin marketing the H101 virus for treating
head and neck cancer. This information will be used in our
paper to further explain how the ONYX-H101 virus is
currently being used in other countries as the main treatment
for cancer and should also be implemented in the United
States.
[4] Kelly, Elizabeth, and Stephen J. Russell. "History of
Oncolytic Viruses: Genesis to Genetic Engineering."
Nature.com. Nature Publishing Group, n.d. Web. 13 Jan.
2016.
http://www.nature.com/mt/journal/v15/n4/abs/6300108a.htm
l.
This article from the Nature Publishing Group and it
offers specific, qualitative history about oncolytic viruses.
The authors aim to provide an in-depth description of the
methods for virus propagation in the 1950-60s, and how the
advancement in technology has allowed for a significant
progression in the science. We will use this journal in a
section of our paper that explains how technology has
allowed for virotherapy to grow and become safe.
[7] Latvian State Agency of Medicines Registry
http://www.zva.gov.lv/zaluregistrs/?iss=1&lang=en&q=Rigvir&ON=&SN=&NAC=on
&RN=&ESC=on&AK=&SAT=on&RA=&DEC=on&LB=&
PIM=on| accessed 21 January 2015
This is the Medicinal Product Register of the Republic
of Latvia, where the ONYX-015 H101 virus has become
approved as a viable medical treatment option for patients’
with cancer. The ONYX-015 H101 is an experimental
oncolytic virus created by genetically engineering the
adenovirus that is implemented in Latvia, and other
countries, to use in replacement of chemotherapy and
University of Pittsburgh Swanson School of Engineering 2
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radiotherapy to treat cancer. This information will be used in
our paper to discuss how other countries are using
alternative methods to curing cancer.
[2] "Pancreatic Cancer Survival Statistics." Pancreatic
Cancer Survival Statistics. Cancer Research UK, 15 May
2015.
Web.
11
Jan.
2016.
http://www.cancerresearchuk.org/healthprofessional/cancer-statistics/statistics-by-cancertype/pancreatic-cancer/survival#heading-Zero.
Scientists from the Cancer Research UK in England
recently discovered the statistical survival rate for pancreatic
cancer, which arises when cells in the pancreas begin to
multiply and form a mass. These statistics show how the
current cancer treatments currently used are not sufficient
enough to kill the cancer cells. We will include this
information within our abstract as evidence that virotherapy
is a more practical and effective treatment.
[8] Russell, Stephen J., Kah Whye Peng, and John C. Bell.
"ONCOLYTIC VIROTHERAPY." N.p., n.d. Web.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888062/
This article from the National Institutes of Health
discusses the challenges scientists face to select the best
oncolytic virus platforms and engineered derivatives, to
transiently suppress the immune system to maximize both
virus spread and anticancer immunity. This information will
be incorporated in our background section of oncolytic
virotherapy.