Oncolytic viruses can be used to treat cancer by infecting and killing cancer cells. They have the potential advantages of direct killing, inducing anti-tumoral and anti-viral immunity, and eliciting innate and adaptive immune responses. However, their effects may vary between individuals and they can be cleared by the immune system. Oncolytic viruses work by hijacking the cancer cell's protein production, triggering "danger signals" and releasing viral progeny to infect neighboring cells, which stimulates anti-cancer immunity locally and systemically.

1. Introduction
You might consider both viruses and cancer as your enemies but how about partnering with one of them to fight the other. Thanks
to the novel immunotherapy, oncolytic viruses made this possible to say the least. Cancer cells frequently have weak antiviral
defenses render them vulnerable to infection. Oncolytic viruses employ viruses to infect and kill cancer cells. Recently, pre-
existing cancers have been targeted and attacked by viruses. These oncolytic viruses represent a promising method for treating
cancer for a number of reasons. Scientists excelled in modifying these natural viruses to have beneficial traits to infect healthy
cells, and they have the potential to burst cancer cells after infection, destroying the cancer cells and releasing cancer antigens.

2. Advantages
• A direct killing potential (oncolysis)
• The capacity to induce two new overlapping, but
distinct, immunities: anti-tumoral and anti-viral.
• OV infection and oncolysis naturally elicit both
innate and adaptive immune responses (required for
long-term anti-tumoral immunity); at the same time,
the viral infection prompts an anti-viral response.
Disadvantages
• Oncolytic virotherapy does not have a stable
curative effect in different individuals because
everyone’s physical environment is not the same
• OVs are too easy to be cleaned by the body’s
immune system.
• The biosafety of oncolytic virotherapy deserves
further research, especially for people with low
immunity.

3. The CRISPR-Cas9 system has
been used successfully in
creating mutations with high
efficiency in the target region
of AdV and HSV-1
Unfortunately, this process has
a homologous recombination
efficiency of less than 1% and
often the selection marker is
randomly inserted elsewhere
into the virus genome and,
subsequently, drops out upon
virus expansion
The conventional method for
generating tumor-targeted OVs
with large genomes is based on
homologous recombination
using a shuttle vector, either in
bacteria or in mammalian cells

4. Sarcoma
Bladder
cancer
Solid
tumors Melanoma
Ovarian
cancer
Clinical applications

5. It is important to know that what makes OV
administration attractive is the capacity to
induce two new overlapping, but distinct,
immunities: anti-tumoral and anti-viral. OV
infection and oncolysis naturally elicit both
innate and adaptive immune responses
required for long-term anti-tumoral
immunity); at the same time, the viral
infection prompts an anti-viral response.
When selecting for the appropriate OV
treatment strategy, intrinsic characteristics
should be taken into consideration. Each OV
family will exhibit unique genome
complexities, replication mechanisms, lytic
properties. OVs will exhibit distinct tumor
tropisms.
The tumor microenvironment (TME) typically
exhibits an immunosuppressive milieu. Tumors
generally secrete soluble immunosuppressive
mediators, including nitric oxide and cytokines
such as interleukin (IL)-10 and transforming
growth factor-β (TGF-β). The multiple and
complementary mechanisms of action of OVs will
be successful only if they ultimately reverse the
local immunosuppression and create a sufficient
pro-inflammatory and pro-immune environment.
.
Relation to the immune system

6. Following administration, the OV will infect
tumor cells and hijack the cell’s protein
synthesis, promoting the production of viral
macromolecules, but it will also trigger
the expression and recognition of “danger
signals that culminate with the release of
cytokines and damage-associated molecular
patterns (DAMPs). Additionally, OVs cause
cancer cell killing by promoting cell lysis, a
process known as oncolysis, followed by the
release of infectious viral progeny that
spread to surrounding tumor cells. All of
these processes contribute to the stimulation
of the innate and adaptive anti-cancer
immune responses locally and systemically.
Besides oncolysis and anti-tumoral
immunity, some OVs have been shown to
have potent anti-angiogenic effects by
triggering an acute disruption of the tumor
vasculature
OV infection of cancer cells changes how
antigens are presented to the immune system
and is the key reason why novel anti-tumoral
immunity is elicited. The cell-intrinsic
aberrations of OV-infected cancer cells are
linked to how they are perceived by the
elements of the innate and acquired immune
systems. However, following the virus
colonization of the tumor, the host anti-viral
immunity will become activated and
mobilized to restrict virus replication and
spread, culminating in viral clearance and
elimination of the therapeutic effect.8 Thus,
the effective “time window” for most OVs to
activate anti-tumoral immunity is generally
within the first 1–2 weeks of administration,
before the virus is cleared.

7. OV includes direct
oncolysis or cytotoxicity
toward the cancer cells
Indirect induction of
bystander effects
(including the destruction
of tumor blood vessels)
and immunotherapeutic
toward tumors
Mechanism of action

8. Oncolytic viruses
can
Hijack the tumor
cell’s protein
factory
induce of immune
response
destroy tumor
blood vessels
Tackles structure
of tumor
microenvironment
Release of damage-
associated molecular
patterns (DAMPs)

9. Cell Carriers are:
Antigen specific T-cell
Mesenchymal
stem cells
Blood outgrown
endothelial cells
Cytokine
induced Killer
cell
Nonocarriers
can also be used

10. Genetically Engineer
Oncolytic Virus
Combination of
Radiotherapy With
Oncolytic Viral Therapy
Combination of
Chemotherapy With
Oncolytic Viral Therapy
Combination of Immune
Checkpoint Inhibitors With
Oncolytic Viral Therapy
To enhance the
therapeutic
effect