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Hello,
my name is Kevin Harrington.
I work at the Institute
of Cancer Research in London.
I have a long-standing interest
in the development
of oncolytic viruses
as cancer therapies.
Today, I will be discussing
Talimogene Laherparepvec:
a First-in-Class
Oncolytic Immunotherapy.
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Here are my disclosures.
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For many years,
we have been interested
in the use of viruses
as potential therapies for cancer.
And on this slide, you can see
a small number of viruses
that have been
in active preclinical
and clinical evaluation
in the last two decades.
The rest of this talk
is going to focus on a single
example of this
which is the Herpes simplex virus,
which is now a registered therapy
with an approval
for the treatment of melanoma
in the USA, in Europe,
and in Australasia.
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The principle of oncolytic viruses
rests on the fact
that certain viruses are capable
of infecting normal cells
where they will trigger
a potent antiviral response,
mainly based around
interferon signaling.
And this antiviral response
will shut down viral replication
and then as an additional
safety measure
will frequently trigger
the cell into apoptosis,
thereby protecting the host
against productive viral infection.
In certain situations,
these same viruses,
if they find themselves
infecting a cancer cell,
will be able to replicate.
And this is usually
based around the fact
that tumor cells frequently
lack normal
antiviral interferon
signaling responses.
As a consequence,
the productive replication of virus
is capable of mediating a process
of tumor lysis so called oncolysis,
leading to the release
of daughter virions,
which have the potential to cause
a cycle of ongoing replication
and infection in other tumor cells,
potentially leading
to a cancer specific infection.
