This information is directly
paraphrased from
Cell Genesys Inc., a company
focused on the
development and commercialization of novel biological therapies for patients
with cancer. If I had to put my money on a future cancer cure with the
best chance for success, this is the technology I'd pick.
Oncolytic ("onco" meaning cancer, "lytic" meaning "killing") viruses
represent an innovative cancer therapy known as "virotherapy"—a therapy that
seeks to harness the natural properties of viruses to aid in the fight against
cancer.
The notion of using a virus in the fight against cancer has existed for
many decades. In the 1940s and 50s, studies were conducted in animal models to
evaluate the use of viruses in the treatment of tumors. In 1956, one of the
first human clinical trials with an oncolytic virus was conducted in patients
with advanced stage cervical cancer. Although the results were promising,
research in this arena was delayed due to the lack of technologies needed to
purify viruses and to safely deliver the viral treatment. It was not until
1991, following a publication in Science magazine about a study conducted at
Georgetown University that used the herpes simplex 5 virus for the treatment
of brain cancer, that new attention was focused on virotherapy.
In short, oncolytic viruses are human viruses that infect and replicate in
cancer cells, destroying these harmful cells and leaving normal cells largely
unaffected. Like all viruses, oncolytic viruses seek to penetrate a host cell
and "trick" it into replicating more of the virus until ultimately, it bursts.
However, unlike other viruses, oncolytic viruses seek only to replicate in
cancer cells.
Research is currently being conducted by institutions around the world
using both "non-engineered" and "engineered" viruses to evaluate their use in
the fight against multiple types of cancer. Non-engineered viruses are
naturally occurring viruses that innately and preferentially target certain
types of tumor cells. Some non-engineered viruses include the Newcastle
Disease Virus, Autonomous Parvovirus, and the Reovirus. Conversely, some other
viruses which do not normally target cancer cells are "re-engineered" to do
so. Scientists genetically modify the virus to replicate within specific types
of cancer cells. Today, three main approaches are being explored in the
development of engineered tumor-specific oncolytic viruses:
● Selective Targeting—Capsid Protein
Modification: The capsid protein, the external surface of the virus, is
modified so that the virus will specifically target cancer cells, completely
avoiding normal cells. The virus would then replicate within the targeted
cancer cell, ultimately leading to cell death.
● Selective Replication in the Absence of an
Antitumor Gene: The virus is genetically modified so that it will replicate
only in the absence of a gene believed to inhibit tumor cell growth, such as
P53. While the virus "passes through" normal cells, it is triggered to
replicate in cancer cells that do not exhibit an antitumor gene, ultimately
leading to cancer cell death.
● Selective Replication in the Presence of Unique
Tumor Cell Characteristic: The virus is genetically modified so that it will
replicate only in the presence of a characteristic (e.g. an antigen) unique
to the specific type of cancer. While the virus passes through normal cells,
it is triggered to replicate in cancer cells that exhibit a specific
characteristic, ultimately leading to cancer cell death.
Examples of viruses that are re-engineered to work in this fashion include
the adenovirus, the herpes simplex virus-1, influenza, and the vaccinia virus.
Oncolytic viruses use multiple mechanisms of action to kill cancer cells.
Once the virus infects the tumor cell, it compromises the cell's natural
defense mechanisms, giving the virus extra time to thrive. The virus then
begins to replicate. The virus continues to replicate until finally the tumor
cell can no longer contain it and "lyses" (bursts). The tumor cell is
destroyed and the newly created viruses are spread to neighboring cancer cells
to continue the cycle. It is important to remember that all oncolytic viruses
are intended to replicate only in cancer cells and to pass through normal
tissue without causing harm. Once all the tumor cells are eradicated, the
oncolytic virus no longer has a viable site in which to replicate, and the
immune system eventually clears it from the body.
Clinical data suggest that oncolytic viruses will offer significant
therapeutic advantages over existing cancer therapies such as chemotherapy and
radiation. The primary benefits identified to date include the following:
● High Therapeutic Index: Compared with
traditional therapies, oncolytic viruses have been shown to have a high
therapeutic index. In some instances, the therapeutic index of such viruses
has been found to be as high as 100,000 to one. In other words, for every
100,000 tumor cells that are killed, only one normal cell is killed. This is
significantly higher than the therapeutic index commonly seen with
chemotherapy—six to one—and may result in greater efficacy with fewer side
effects.
● Better Antitumor Efficacy due to Viral
Replication: Unlike some traditional therapies that are cleared from the
body within a specific amount of time (e.g. chemotherapy), oncolytic viruses
are engineered to proliferate and remain in the body until all of the cancer
cells are destroyed. This self-proliferation reduces the need for extensive
re-treatment and results in greater efficacy and patient convenience.
● Synergistic Antitumor Activity with Other
Cancer Therapies: Some oncolytic viruses have been shown to work even better
when used in combination with conventional cancer treatments such as
radiation and chemotherapy.
This sounds like fascinating stuff to me. There is
something appealing about the notion of sending in small insurgencies of nano-troops
to attack cancer cells from the rear, at their own level of operation. I
always thought of cancer cells as actually being "improved" versions of normal
cells, overcoming the natural order of individual cell old age & death,
multiplying efficiently and taking over territory quickly and effectively.
That is, until the host dies -- at which time cancer doesn't seem so smart,
after all. In this respect, a cancer cell is like a newly evolved
viral or bacterial strain, one that hasn't yet learned to improve its
long-term reach and effectiveness by not being so virulent to its host.
What other replicating life-form is so blasted efficient at multiplying and
spreading? Of course: viruses! It sounds like a cool idea to
pit them against each other.
Back to Loose Ends...
See also my page on
bacteriophages.
You can argue whether or not viruses are truly
life-forms. Viruses certainly straddle the gap between life and
non-life. They do replicate and contain the genetic material required to do
so. They have simple physical accoutrements to latch onto a cell
wall and inject their genetic material into a cell. That's about all
they do. Their structure is extraordinarily non-complex, almost
mechanical in its appearance and operation. It begs the question as to
what life really is. But because I personally never replicated, I
suppose you could make a case that a virus has a stronger basis for being
considered alive than I do!
