Sciences de la Santé
The New Castle disease virus; a fowl infecting
microbe and non-pathogenic to humans; can bind
to human cells via HN (Hemagglutinin and Neu-
raminidase). It can activate Caspases (Cysteine
Aspartic acid- Specific ProteASES) in cancer cells.
These molecules not only work as initiators and
executioners of cell death, but also have the abi-
lity to cleave Livin. A member of the Inhibitor of
Apoptosis Protein (IAP) family. Livin is associated
with poor prognosis when highly expressed in
melanoma. Once cleaved, Livin becomes parado-
xically proapoptotic, enhancing furthermore the
cellular death effect of this OV.
It is uncontestable that oncolytic viruses have
proved their usefulness. Nevertheless, they still
have their limits. First, their testing in animal mo-
dels can sometimes wrongly predict the outcomes
of clinical trials.
Indeed, viruses are either tested in xenografts
(human tumor tissue grafted in an animal) im-
planted in an immunocompromised mouse. Or
an immunocompetent one in which a tumor has
been induced in its own tissue. Both cases may
not foresee the results found in clinical trials on
human subjects.
Another limitation, is that they still induce both
an innate and an adaptive immune response.
Through the former, it has been observed that OVs
administered intravenously can bind to platelets
and are later cleared in the liver by Kupffer cells.
Through the latter, many humans are already im-
munized to viruses (50–80% possess neutralizing
antibodies against HSV and almost 90% against
Reovirus). This makes their administration exclusi-
vely intratumoral, intraperitoneal or intrapleural.
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Hiver 2018
The intensive research done in this field and the
little progress encountered (only two viruses ap-
proved for treatment) makes it clear that onco-
lytic viruses aren’t very effective as an isolated
treatment for cancer. They can work in synergy
with others lines of treatment.
Many clinical trials are investigating these com-
binations. For instance, infecting immune host
cells with an OV ex vivo, then injecting it back to
the patient can help detour the antiviral immune
defenses and deliver the virus safely to the tu-
mor bed. This is referred to as the “Trojan horse”
strategy. The difficulty lies in finding the ideal
cell carrier for the patient and the tumor. Further
research is being done in this regard. Another
combination that has potential, is a viral bacterial
combined therapy. In such a combination, the vi-
rus infects an intracellular and anaerobic bacteria.
This bacteria would have enhanced chemotaxis
towards tumors and would be lured by their hy-
poxemic regions that result from an undeveloped
vascularization. Once inside, the virus would be
delivered safely and can infect the totality of the
tumoral tissue.
These are one of the alluring prospects virothe-
rapy offers in the fight against cancer, humanity’s
immortal enemy. The success of T-VEC with mela-
noma seems to be a promising start to many other
achievements. Especially, that this particular can-
cer is one of the most aggressive ones. T-VEC has
opened a door to many possibilities: involving
this same agent in a combination with immuno-
therapy (anti PD1 and anti CTLA-4 therapy) is cur-
rently being tested. More has yet to come.