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REVIEW ARTICLE
Oncolytic Virotherapy
Daniel Y. Sze, MD, PhD, Tony R. Reid, MD, PhD, and Steven C. Rose, MD
ABSTRACT
Oncolytic virotherapy is an emerging technology that uses engineered viruses to treat malignancies. Viruses can be designed with
biological specificity to infect cancerous cells preferentially, and to replicate in these cells exclusively. Malignant cells may be
killed directly by overwhelming viral infection and lysis, which releases additional viral particles to infect neighboring cells and
distant metastases. Viral infections may also activate the immune system, unmask stealthy tumor antigens, and aid the immune
system to recognize and attack neoplasms. Delivery of live virus particles is potentially complex, and may require the expertise
of the interventional community.
Infections and cancer are usually thought of as unrelated
diseases. However, viruses are now implicated as causative
factors in numerous human malignancies, including cervical, hepatic, oropharyngeal, and some lymphatic cancers, and the proportion of all cancers caused by infectious
agents is now estimated to be more than 20% (1). In
addition, the host responses to viral infections and to
cancers share numerous immunologic and genetic commonalities. As our understandings of malignancy and of
infection improve, new tools are emerging to exploit the
molecular specificities of viruses to address malignancy.
Specifically, viruses capable of infecting and killing cancers
are being developed in a field referred to as oncolytic
virotherapy (2–5). This review will introduce the biological
concepts of oncolytic virotherapy, summarize the current
From the Division of Interventional Radiology (D.Y.S.), Stanford Cancer
Center, Stanford University School of Medicine, Stanford; Division of Interventional Radiology (S.C.R.), University of California, San Diego, Health
Sciences, San Diego; Division of Medical Oncology (T.R.R.), Moores Cancer
Center, University of California, San Diego, La Jolla, California. Received
March 1, 2013; final revision received and accepted May 12, 2013. Address
correspondence to D.Y.S., Division of Interventional Radiology, Stanford
University Medical Center, H-3646, 300 Pasteur Dr., Stanford, CA 943055642.
D.Y.S. is a scientific advisory board member of Jennerex Biotherapeutics (San
Francisco, California) (pertinent); a speaker for W. L. Gore and Associates
(Flagstaff, Arizona); a consultant for Sirtex Medical (Lane Cove, New South
Wales, Australia), Nordion (Ottawa, Ontario, Canada), and Biocompatibles; an
advisory board member of Lunar Design (San Francisco, California), Surefire
Medical (Westminster, Colorado), Treus Medical (Redwood City, California),
and Radguard (Los Altos, California); and a shareholder in NDC, Inc. (Fremont,
California; not pertinent). S.C.R. is a proctor and speaker for, and minor
stockholder in, Sirtex Medical; a medical advisory board member of, and
minor stockholder in, Nordion; a consultant for Terumo (Somerset, New
Jersey); a medical advisory board member of AngioDynamics (Latham, New
York); and a speaker and consultant for, with a pending patent with, Surefire
Medical (not pertinent). T.R.R. has not identified a conflict of interest.
& SIR, 2013
J Vasc Interv Radiol 2013; 24:1115–1122
http://dx.doi.org/10.1016/j.jvir.2013.05.040
state of the art, and describe the past and potential future
roles to be played by interventional radiologists.
HISTORY
For more than a century, there have been documented
miraculous remissions of advanced cancers temporally
related to viral syndromes. Dock (6) reported in 1904 a
case of leukemia in a woman who had a complete but
temporary remission after a bout of an upper respiratory
infection, presumed to be influenza. Other authors reported similar observations of spontaneous remissions of
leukemias and lymphomas after infections such as chicken
pox, measles, or hepatitis (7). The dominant theory at the
time was that the remissions were caused by a direct and
specific infection of tumor cells by the invading infectious
agent, even though viruses were just in the process of being
discovered and characterized.
In the ensuing decades, viruses were isolated, characterized, and photographed by electron microscopy. The
structure of viruses was elucidated, consisting of a core of
RNA or DNA, which can be single- o double-stranded,
surrounded by a protein coat. Some viruses have an outer
envelope of lipids. Viruses are not independent life forms,
because they require the cellular infrastructure of a host
to replicate and propagate. Viruses are often specific to
a certain host species, and often to a specific type of
host cell.
Early work showed that some strains of viruses grew in
murine tumors, but infection caused the tumors to be less
malignant (3). These observations, along with the empirical observations of spontaneous remissions in infected
patients, led to the first preclinical experiments exploring
infectious viral agents as potential treatments for cancer.
Initial attempts that used wild-type murine viruses against
murine tumors were published in the 1940s (8). When
given intravenously at high doses, these live viruses were
able to show antineoplastic activity, but also exhibited
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lethal toxicity. Early human trials that used wild-type
viruses, often with unpurified sera or tissue culture supernatants administered intravenously, intratumorally, intraarterially, intramuscularly, or inhaled, gave enticing hints of
efficacy, but were severely limited by toxicity (7).
With the advent of human cell culture in the 1940s
and 1950s (9) and molecular biology in the 1970s, the
ability to study and to alter genetic material in vitro
became feasible. The concept of genetic therapy was a
logical consequence, and a new field arose addressing
diseases with identifiable genetic abnormalities by
alteration of existing genetic material or introduction
of new genetic material. Viruses were adopted as highly
evolved and efficient couriers of this genetic material,
since eons of evolution had resulted in biochemical
specificity for host receptivity. If these couriers could
be engineered to carry toxic or lethal or normalizing
genetic material, they could serve as Trojan horses to kill
or neutralize targeted cells, and this formula constituted
the large majority of earlier gene therapy research on
cancer treatment (10). These studies assured patient safety by using viruses that were engineered to be replication-incompetent, unable to reproduce themselves and to
spread.
In parallel with developing technology to use viruses
as Trojan horses carrying exogenous genetic material,
others refined decades-old methods of live vaccine design
to develop viruses that retained infectious capabilities
while exhibiting weakened or attenuated pathogenicity.
Rather than using these viruses as couriers of genetic
materials, these viruses could be engineered to be
selectively infectious and cytotoxic, and the concept of
using viral infections as treatment of cancer was revisited
(11). The unacceptable toxicity in the earlier murine and
human experiments that used wild-type viruses could
now be diminished by deactivating individual genes in
the viral genome, rendering the viruses attenuated in
pathogenicity. Certain genes would need to be retained
to maintain antineoplastic efficacy, but others could be
inactivated to impart a margin of safety. Many firstgeneration oncolytic viruses were adapted from viruses
selected for mutations or attenuations for purposes of
serving as potential vaccines (12). These were selected to
retain enough infectiousness to attack cancer cells and to
evoke an immune response in the host, but caused
tolerable morbidity. Some of these viruses were also
found to have selective infectious capabilities, able to
infect transformed or cancerous cells more effectively than
normal cells. The observation of biochemical specificity of
infectiousness led to numerous academic and commercial
enterprises investigating feasibility and safety of engineering viruses to be used as cancer treatments, entering
human clinical trials by the 1990s (7).
The promise of oncolytic virotherapy is no longer a
purely academic exercise. Although there are no
approved agents in the Western world, the Chinese State
Food and Drug Administration approved an engineered
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human adenovirus (Oncorine; Shanghai Sunway Biotech,
Shanghai, China) for treatment of head and neck carcinoma in 2005 (13). Dozens of clinical trials are under way,
and the rate of publication of manuscripts on oncolytic
virotherapy has now surpassed that on viral cancer gene
therapy (4). The biotechnology and pharmaceutical
company Biogen Idec (Weston, Massachusetts) purchased BioVex for its oncolytic platform in 2011 for $1
billion, heralding recognition of medical as well as
financial viability of the field (14). The achievement of
positive results in their phase III trial of the treatment of melanoma was recently announced, although
the results of the trial have not yet been published (15).
Most recently, Jennerex Biotherapeutics (San Francisco,
California) received orphan drug designation by the
United States Food and Drug Administration for their
oncolytic vaccinia product Pexa-Vec, which is in phase IIb
trials as a treatment for hepatocellular carcinoma (16).
RATIONALE AND MECHANISMS OF
ACTION
The field of oncolytic virotherapy uses viruses as treatment agents against cancers. Viruses coevolved with
their hosts, and developed biological specificities and
activities that allow them to infect and attack specific
cells and organisms. Tailoring the behavior of viruses
can result in safer agents, as well as more efficacious or
more biologically specific agents. Several characteristics
of viruses can be exploited (Fig 1). These include the
ability to replicate, or multiply, in the host cell, thereby
enabling self-amplification and eliminating the need to
infect every target cell at the time of initial treatment.
Another useful characteristic is the specificity for a
certain type of cell or cell receptor, such as an epithelial
or neural cell. The genetics of viruses may interact
differently with normal cells than with malignant cells,
but the host response to viral infections shares many
humoral and cell-mediated processes with the host
response to cancer. It has also been proposed that cancer
stem cells, resistant to conventional therapies, may
exhibit special susceptibility to viral infection (17).
The original oncolytic effects of viral infection were
attributed to a mechanism of action involving direct
infection and cell lysis. Viruses hijack a cell’s protein
factory, disabling its production of host products in
favor of viral products, which may also be intrinsically
cytotoxic. The terminally infected host cell eventually lyses, releasing new virions capable of infecting other cells
in a “bystander” effect, amplifying and propagating
the initial effect of infection (18). In addition, lysis of the cell may release and uncloak tumor antigens
that were previously sequestered in the intracellular
milieu.
Whether by uncloaking tumor antigens or by triggering an immune response to infection, viruses can act
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Figure 1. An oncolytic virus, represented by black hexagons, attacks a cancerous cell (a). As a result of a natural tropism for the cell
type or a specificity for a tumor-related cell surface antigen or receptor, the virus enters the malignant cell more readily than it would
enter into a normal cell (e), which may not exhibit the same receptivity to infection. Upon infecting the malignant cell, the permissive
nature of the cell that allows malignant genetic material to propagate also allows unchecked replication of the virus (b). An infection of a
normal cell (f) is abortive as a result of the cell’s ability to recognize and to destroy abnormal genetic material. The infected cell (b) will
produce viral proteins that are antigenic and may alert the immune system, and, if the virus is genetically armed, the cell may produce
cytokines and other signaling chemicals to activate the immune system. The infected cancer cell is eventually overwhelmed by the viral
infection and lyses, releasing new viral particles locally to infect neighboring malignant cells (c). Lysis releases new viral and tumorrelated antigens, which may be recognized and attacked by the immune system, represented here by a lymphocyte (L). Lysis-related
viremia may result in infection of distant metastases (d), transforming a locoregional effect into a systemic effect. Activation of the
immune system with elevation of systemic cytokine levels and activated leukocytes further enhances the systemic effect. Parts of the
immune system may also develop memory and learn to recognize tumor antigens, potentially providing a more durable defense
against residual and recurrent disease.
as immunomodulators or even tumor vaccines. Infected
tumors may become inflamed, releasing an array of
cytokines and becoming suffused with immune cells,
including cytotoxic T lymphocytes, natural killer cells,
dendritic cells, and phagocytic cells, and can become
exporters of these signals and cells (19). Theoretically, an
infection could function as an inoculation with development of memory against tumor antigens. In addition,
generation of cytokines and alteration of blood flow
and oxidation potential could also affect a tumor’s susceptibility to radiation or chemotherapies (20). Systemic
viremia and upregulation of the innate and adaptive
immune systems can infect and treat distant metastases as well, turning a locoregional therapy into a combination systemic therapy.
In addition to exploiting the natural infectious capabilities and immunogenicity of viruses, these properties can
also be augmented by deleting, adding, or replacing genes
into a virus’s payload. Many later-generation oncolytic
viruses have been engineered (ie, armed) to express
exogenous genes. Viruses may be armed to produce
cytokines such as human tumor necrosis factor or granulocyte–macrophage colony-stimulating factor (21), even
further heightening the host’s response to the infection.
Because of the fixed and small size of a viral particle, the
size of its payload or of its genetic arming is limited.
SPECIES-SPECIFIC MECHANISMS
An unfathomable variety of viruses have evolved, with
varying degrees of human pathogenicity and specificity.
Some viruses are naturally oncotropic, especially infectious in host cells with cancer-related mutations. These
viruses include reovirus, parvovirus, varicella virus, and
Newcastle and Sindbis viruses (5). Others may exhibit
specificity to tumor environment or stroma, including
herpes, measles, and Newcastle viruses, and reoviruses.
Some viruses exhibit specificity for surface receptors. For
instance, adenoviruses, polioviruses, measles viruses, and
varicella viruses have recognized receptors necessary for
cellular adhesion, internalization, and pathogenicity.
Many adenoviruses can infect only one mammalian
species. Some can infect only epithelial cells of a
species. Pathogenicity of adenoviruses relies on their
ability to infect normal respiratory epithelial cells in a
particular host, which may in turn rely on the virus’s
ability to counteract the host cell’s defenses. However,
some of the genes necessary for this pathogenicity may
be attenuated or deleted, rendering the virus incapable of
infecting normal cells with normal defenses. However,
malignant cells may lack normal defenses, and therefore
remain susceptible to infection by the attenuated virus.
Deletion of viral genes necessary to counteract host
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defenses is a strategy that has been applied in adenoviruses, herpesviruses, and vaccinia viruses (22).
Other oncolytic viruses may be engineered with specific
promoters. For instance, experimental adenoviruses and
herpesviruses have been created that specifically recognize
and attack cells that produce α-fetoprotein or prostatespecific antigen (23). Other strategies for oncolytic virus
design include modification of the viral surface protein to
alter its specificity, which has been attempted with measles
and polio viruses. Finally, some viruses have been
engineered to target tumor vascularity in addition to the
actual tumor cells (24,25).
SAFETY, RISKS, AND REGULATORY
ISSUES
Research involving genetic therapy and viruses has
always been held up to high standards. The lay public
is also acutely aware of potential hazards, fueled by
sensationalized news reports and entertainment. In 2007,
the film I Am Legend, directed by Francis Lawrence and
starring Will Smith, adapted from the novel written by
Richard Matheson, told the apocalyptic story of a lone
survivor after decimation of the world’s population from
an oncolytic measles virus gone haywire. In reality,
numerous levels of genetic engineering, safety precautions, and governmental regulation are structured to
minimize the risk to the general population. In addition
to the Food and Drug Administration, the field is subject
to detailed oversight by the Recombinant DNA Advisory Committee, which reports through the Office of
Biotechnology Activities of the National Institutes
of Health. In addition to scientific and medical experts,
the Recombinant DNA Advisory Committee membership includes bioethicists, patient advocates, and
laypersons. These bodies govern not only the medical
use and investigation of agents, but also the manufacture, purification, quality control, and transport of
preparations.
Many different biological strategies have been implemented to increase the safety of use of oncolytic viruses
(26). The choice of viral species takes into consideration
the natural epidemiology and pathogenicity, including the
prevalence of natural immunity in the human population.
Some species are already part of public health vaccination
programs, so immunity in the general population is
common. Patterns of transmission and viral shedding, as
well as natural predispositions toward spontaneous
mutation, reversion, and genomic integration, are all
taken into consideration during the design of oncolytic
agents. Replication competence and host cell selectivity
can also be selected or tailored. One commonly used
strategy is to use viruses that are naturally infectious only
in species other than humans, such as raccoonpox, Semliki
Forest virus, myxoma virus, or vesicular stomatitis virus.
Another common strategy is to maintain or to augment a
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virus’s susceptibility to antiviral therapies such as
nucleoside analogues (eg, acyclovir, ganciclovir).
Numerous questions about safety remain controversial. For instance, comorbidities such as cirrhosis, heart
disease, pulmonary disease, and coagulopathies could
theoretically be exacerbated by oncolytic virotherapy.
Interactions with other viruses such as hepatitis B or C
viruses, HIV, Epstein–Barr virus, or cytomegalovirus
could have unexpected consequences, including possible
favorable suppression of these other pathogens (27).
However, some patients with pre-existing chronic viral
infections may also be receiving antiviral therapy, which
could interfere with viral oncolysis.
Evaluation of response to oncolytic virotherapy is also
poorly defined in the diagnostic radiology realm. Early
clinical trials were partially compromised by the phenomenon of “pseudoprogression,” whereby treated
tumors increased in size and enhancement heterogeneity,
likely from infection-related inflammation and edema
(28). Similarly, initial increased metabolism portrayed by
[18F]fluorodeoxyglucose positron emission tomography
was observed in successfully treated lesions that later
regressed, further confusing the radiographic response
evaluation (29). Novel molecular markers may need to
be developed for accurate clinical assessment.
PUBLISHED CLINICAL TRIALS
The Table (25,27–65) presents a partial list of published
human clinical trials investigating oncolytic virotherapy.
Nearly every major cancer type and organ is being
investigated, and an ever-increasing roster of different
virus species is developing in this field that echoes the
search for new antibiotics, in which natural biological
warfare is being studied along with the genomics and
pathways of each combatant (66–70).
FUTURE DIRECTIONS AND POTENTIAL
ROLES OF INTERVENTIONAL RADIOLOGY
The fact that oncolytic virotherapy has not yet entered
the mainstream of medicine reflects numerous technical
and biological challenges. The vast array of different
viral species and specificities, and the even more vast
array of possibilities of how to engineer viruses and arm
them, require a tremendous amount of additional
research. Other factors that have been shown to play
roles but have not been optimized include manipulation
of the immune system. Suppression of the immune
system may potentiate infectiousness by overriding preexisting immunity against a virus to which the subject
has already been exposed. However, at least a portion of
the efficacy of a virus may require a functional immune
system, and concomitant administration of immunosuppressant agents such as corticosteroids can actually blunt
the oncolytic effect of the virus (71). Over time, repeated
Attenuation/Selectivity
Armed
Cancer(s) Treated
Delivery
Refs.
ONYX-015
Onyx
E1B deletion
–
Head/neck, mCRC,
pancreas,
IT, IA, IV, IP
28,30–35
glioma, ovarian,
’
GM-CSF
sarcoma
Bladder
Intravesical
36
CG7870, CV706
Cell Genesys
PSA promoter, E3 deletion
–
Prostate
IT
37,38
Sunway Biotech
Sunway Biotech
E1B deletion
E1B deletion
HSP70
–
Mixed
Mixed
IT
IT
39
40
Introgen
hTERT promoter
–
Mixed
IT
41
Oncos
–
RGD-4C, E1A deletion, E2F promoter
Telomerase-positive
–
GM-CSF
Mixed
Head/neck
IT
IT
42
43
Telomelysin
ICOVIR-7
KH901
Ad5-CD/Tkrep
–
E1B deletion
ADP, cytosine deaminase, TK
Prostate
IT
44
Ad5-D24-RGD
Ad5/3-D24-GM-CSF
–
–
Integrin tropism, p16/Rb
Integrin tropism, p16/Rb
–
GM-CSF
Gynecologic
Mixed
IP
IT
45
46
CGTG-401
–
hTERT promoter
CD40 ligand
Mixed
IT
47
HSV-1 (dsDNA)
NV1020
MediGene
ICP34.5, other deletions
–
mCRC
IA
29,48
–
Natural multiple mutations
–
Pancreatic, breast
IT
49
JS1/34.5-/47-/GM-CSF
Oncovex
–
BioVex/Biogen
ICP34.5 deletion
ICP34.5 deletion
GM-CSF
GM-CSF
Head/neck
Melanoma, others
IT
IT
50
51,52
HSV1716
Virttu Biologics
ICP34.5 deletion
–
Oral SCC, glioma,
IT
53–55
Glioma, melanoma
IT, IV
56,57
HF-10
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E2F-1 promoter
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Cell Genesys
August
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H103
H101
Number 8
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Virus (Type)/Agent
Adenovirus (dsDNA)
Volume 24
Table . Summary of Published Clinical Trials Investigating Oncolytic Virotherapy in Humans (25,27–65)
melanoma
Reovirus (dsRNA)
Wild-type, natural
–
Wellstat Biologics
Naturally attenuated
–
Mixed
IV
58
–
Six gene variations, one cycle replication only
–
Glioma
IV
59
RT3D (Reolysin)
Oncolytics Biotech
Newcastle (ssRNA)
PV701
NDV-HUJ
Measles (ssRNA)
MV-CEA
–
CEA marker
–
Ovarian
IP
60
Edmonston–Zagreb
–
Commercial vaccine
–
Cutaneous TCL
IT
61
Picornavirus (ssRNA)
SVV-001
–
Neuroendocrine tropism
–
Neuroendocrine
IV
62
Jennerex Biotherapeutics
TK deletion
GM-CSF
HCC, melanoma, others
IT, IV
25,27,63–65
Vaccinia (dsDNA)
JX594
1119
CEA = carcinoembryonic antigen, dsDNA = double-stranded DNA, dsRNA = double-stranded RNA, GM-CSF = granulocyte–macrophage colony-stimulating factor, HCC =
hepatocellular carcinoma, HSV = herpes simples virus, IA = intraarterial, IP = intraperitoneal, IT = intratumoral, IV = intravenous, mCRC = metastatic colorectal carcinoma, SCC =
squamous cell carcinoma, ssRNA = single-strand RNA, TCL = T-cell lymphoma.
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Figure 2. The oncolytic virus, represented by black hexagons, must overcome numerous barriers to infect a tumor. If administered
intravenously (IV), some of the virions may adhere nonspecifically to venous endothelium (a). In the bloodstream, other virions may be
neutralized by complement (b), bound by humoral antibodies (c), or adsorbed or engulfed by blood cells, including leukocytes (d),
particularly in patients with pre-existing immunity from earlier exposure to the virus. The virions must then travel through the heart (e)
and lungs (f), where they can also be adsorbed or neutralized. The liver and spleen (g) and the reticuloendothelial system within them
may filter out and eliminate another large proportion of circulating virions. A potentially infectious viral particle that actually reaches the
tumor-feeding vessel could still be adsorbed to the arterial wall (h). It must escape from the vascular space, overcome elevated tumor
interstitial pressure (i), and traverse the extracellular space that contains stromal cells (j) to reach the tumor cells. Intraarterial (IA) and
intratumoral (IT) administration bypass many of these barriers and require the expertise of the interventional community.
administrations of an oncolytic virus result in development of humoral and cellular immunity, so schedule and
route of delivery also require optimization (Fig 2).
Although much of the groundwork originates from
academia and the startup biotechnology industry, the
greatest funding for research and development of biotherapeutics originates from the pharmaceutical industry,
in which oral and intravenous agents are the most prized
and profitable. Oral viral vaccines are available for polio,
rotavirus, typhoid, and rabies, but oral delivery of viruses
is typically much less immunogenic than parenteral
delivery. Many viruses may be inactivated in the gastrointestinal tract by pH extremes and enzymes. Others that
are naturally transmitted via the gastrointestinal tract
may be inadvertently spread to others by fecal–oral or
aerosol routes, raising additional safety issues.
Intravenous delivery is probably the next most convenient and inexpensive route, but has major drawbacks.
As is true of other drugs and agents, systemic delivery is
subject to nonspecific and nontarget binding, such as in
the blood components, vessel walls, lungs, and heart
between the site of delivery and the targeted tumors. In
addition, pre-existing immunity in the form of neutralizing antibodies may inactivate many virions before they
reach their targets. Therefore, in general, large systemic
doses are necessary to provide an adequate inoculum
to the target, and this may increase the risk of a systemic
inflammatory response. Viruses engineered to be extremely specific may ameliorate some of these drawbacks.
A great deal of investment is targeted at increasing tumor delivery and decreasing toxicity of intravenously
administered oncolytic viruses.
Nearly all of the other possible routes of administration of oncolytic viruses lie in the scope of interventional
radiology. The two most studied routes are intraarterial
and intratumoral (ie, interstitial). Other possibilities
include intraportal, intrabiliary, intraperitoneal, intrapleural, organ isolation/perfusion, and retrograde venous
or hydrodynamic (72).
Intraarterial administration shares many advantages
with chemoembolization and radioembolization. Viruses
can be delivered selectively to one organ or subselectively to one tumor. If first-pass uptake is high, systemic
distribution can be drastically diminished. Dwell time
can be adjusted by use of embolization materials or of an
occlusion balloon. Because of the limited blood volume
and target organ volume, neutralization by circulating
antibodies and nonspecific binding to nontarget cells
can be easily overcome by administration of a local excess
of virus. Unfortunately, angiography and intraarterial
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infusions are very expensive, severely straining the limited
budgets of clinical trials and restricting the likelihood of
widespread clinical adoption. Methods to reduce cost and
inconvenience may be necessary for future implementation, such as the use of implantable arterial ports. When
compared with other transarterial therapies such as
radioembolization, the viral selectivity for replication
only within the tumor cells largely eliminates the risks
of nontarget delivery.
The other way interventional radiologists will be called
upon to administer oncolytic viruses is by direct percutaneous intratumoral injection, similarly to how percutaneous
ethanol injection is performed with single- or multiple-tined
needles. The intratumoral distribution of injectate can be
difficult to control and to monitor, but many of the
oncolytic viruses being studied have retained the ability to
replicate, at least in selective environments, which may
result in complete infection of a tumor even if the cells are
incompletely exposed at the time of treatment (73). A
partially infected tumor can propagate the infection by local
release of more virions from lysed cells, which then infect
the neighboring uninfected tumor cells. Compared with
local thermal or liquid ablative techniques in which
limited size and number of tumors are key to efficacy,
the “bystander effect” of oncolytic virotherapy may
dramatically increase the allowable size and number of
tumors that can be treated percutaneously. In addition,
infected cells become factories for new virions that enter the
bloodstream upon cell lysis, resulting in dramatic viral
amplification and systemic viremia, which may result in a
systemic or abscopal effect with infection of distance
metastases. Injection with the use of ultrasound, computed
tomography, or magnetic resonance imaging guidance is
also not without risk and expense, especially with repeated
treatments, which may again affect the commercial
development and clinical adoption of the technology.
CONCLUSION
Oncolytic virotherapy is a complex but promising emerging field within oncology. By exploiting existing pathogens found in nature and genetically engineering them to
be specifically active against neoplastic cells, we are
waging biological warfare against cancer. The mechanisms of action are profoundly different from those of
conventional chemotherapy, radiation therapy, surgery,
embolization, and ablation, and may lead to success in
cases in which tumors are resistant or refractory to
conventional therapy. Safety and efficacy may depend
on mode of administration and may therefore require the
skills of the interventional radiology community.
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