When Cancer Catches the Flu
Rihab FELLAH
Historically, cancer was thought to be caused by viruses, though this remains
true for some types. Today we are using those same agents to fight cancer.
Indeed, virotherapy is at the forefront of the latest advancements in Microbio-
logy, Immunology and Molecular Biology and offers interesting prospects in
the field of oncology.
V
irus have always been known to be remar-
kable microbes. From the Influenza Virus to
the HIV, they have ability to replicate inside
cells by exploiting cellular resources. They can
cause at the end of their reproductive cycle a lysis
of the host cell, which makes them one of nature’s
most effective killers. Science, however, has found
a way to exploit this skill in a more efficient way:
killing cancer cells. Making, therefore, oncolytic
viruses (OVs) the latest leap in oncology and its
armamentarium.
This encounter goes back to the early to mid-20th
century. When regressions of tumoral growth have
been observed in cancer patients suffering from
viral infections. Though these regressions were
temporary and rarely complete, they couldn’t but
spark some hope that a novel cancer therapy has
been discovered. The pursuit of such thought was
halted due to the little understanding researchers
had at the time of carcinogenesis and microbiolo-
gy. Also, the great success that had been demons-
trated by chemotherapy and radiotherapy in trea-
ting cancer prevented it too. Today, in the era of
genetic engineering and recombinant DNA tech-
nology, viruses can be manipulated to be less har-
mful towards healthy cells and to infect tumoral
ones in a specific way. They offer a more targeted
way of treating cancer than that found in chemo
and radiotherapy, with minimal side effects.
In 2015, researchers were at the cutting edge of
cancer therapy when T-VEC–a genetically modi-
fied HSV type 1– became the first oncolytic virus
to be approved by the FDA (Food and Drug Admi-
nistration) and the EMA (European Medical Agen-
cy) for the treatment of unresectable melanoma.
How do oncolytic viruses work exactly? They have
many mechanisms of action.
For starters, OVs whether natural or genetically
engineered and/or modified are, by definition,
viruses that have a particular tropism to cancer
cells. They are incapable of replicating elsewhere.
In fact, many OVs are modified to express mem-
brane proteins/receptors that interact with coun-
terparts found only in tumoral cells. Not forget-
ting that these cells express little self-antigens
such as HLA-1 and do not secrete IFN type I , II or
TNF ( key cytokines for antiviral immunity) when
infected. The lack of effective cornerstones such
as these makes the antiviral immune response
deficient in cancer cells, which explains their sus-
ceptibility to viral infections.
It has been known that cancer cells, escape the
immune system via the expression of certain in-
hibitory immune check points such as PD1 (Pro-
grammed Death 1) and CTLA4 (Cytotoxic T Lym-
phocyte Associated-protein 4).
These molecules are what makes cancer cells to-
lerated by the immune system. Many monoclonal
antibodies targeting them have been developed
and approved as cancer therapies for tumors such
as melanoma and offer, thus, the possibility of a
combined therapy with OVs.
Viruses can also be engineered to produce growth
factors that stimulate antitumoral immunity. It is
the case with T-VEC which expresses GM CSF (Gra-
nulocyte Macrophage Colony Stimulating Factor).
OVs can also be made to activate intracellular pa-
thways that induce apoptosis or deactivate those
responsible for carcinogenesis. This is observed
in Onyx 015, an engineered adenovirus that has
the ability to activate the tumor suppressor p53
and therefore cause oncolysis.
Though this particular virus has not been appro-