One of the major issues still plaguing
cancer research is how to accurately target treatment.
Current therapies don't always do a great job of separating
cancerous cells from normal ones.
In the past ten years or so, hope
of a more efficient solution has been running high as
immunologists began identifying tumour-associated antigens.
At the same time, experts were promoting the idea of
using re-engineered viruses to deliver therapeutic agents,
because viruses are notoriously good at getting into
cells. If there was a way to direct these viruses specifically
to the tumour, it could then deliver the desired therapeutic
product to the right spot.
Now, a team of researchers at the
Mayo Clinic may have brought us one step closer by creating
what they're calling 'hitchhiking viruses.' Though still
in the preclinical phase — the study was conducted
in mouse models grafted with human tumour cells —
the group is confident that the results, published in
the September issue of Nature Medicine, will
go a long way toward overcoming some of the most common
challenges facing gene therapy for cancer.
STOWAWAY
VIRUSES
The approach relies on the use of T cells — the
immune system's primary line of defence against tumours
— to make sure the virus makes it safely to its
target destination. Previous studies of virus-based
therapies hit a brick wall when the virus was injected
systemically, because the immune system recognized it
as foreign and rapidly degraded it. In this case, researchers
capitalized on the observation that retroviral particles
can stick to the surface of T cells and hitch a ride
without being detected, even when the host's immune
system is fully functional.
"The T cells we use are highly
specific to antigens on the surface of the tumour cells.
Five to ten percent of the T cells will end up at tumour,"
said senior researcher Dr Richard G Vile, PhD. Though
this is not a huge proportion, the authors noted that
the virus is then selectively positioned for productive
infection of tumour cells.
And it doesn't make a difference
where the tumour is located. "In a patient with metastatic
disease, it's been a struggle to make vectors that can
home to the tumours," said Dr Vile. But thanks to viral
hitchhiking, that's no longer the case.
SEEK
AND DESTROY
So once the virus has made its way to the tumour cell,
how does it destroy it? Retroviruses are RNA-based viruses
that integrate themselves into the host's genome and
hijack the cell to decode its genes. These particular
viruses have been re-engineered to carry the gene for
an enzyme called herpes simplex virus thymidine kinase
(HSVtk). On its own, HSVtk can't harm the tumour cell,
but when a drug called gancyclovir is added to the mix,
the fate of the tumour cell is sealed.
"Normally HSVtk is completely innocuous,"
said Dr Vile. "But if we give gancyclovir, the enzyme
encoded by HSVtk causes the breakdown of the drug into
a toxic substance that kills the cell."
Not surprisingly, Dr Vile said
that work is not quite ready for use in human patients.
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