The Practical Dream of Cancer Therapies and Vaccines
By Jason Socrates
Bardi
In the field of cancer research, to "cure" is, perchance,
to dream.
To dream of helping the masses who are every year treated
for cancer or of saving over 500,000 Americans who succumb
every year to cancer. But believing in a cure is perhaps to
slip into foolhardy fantasies. We may never find a single
magic bullet that can successfully cure all types of cancer.
Immunology Professor Ralph Reisfeld freely admits to being
a dreamer, although he is also enough of a realist to avoid
using the word cure.
"In science you have to dream a little bit," he says. "My
dream is to prevent cancer."
"And," he adds "if you can't prevent cancer, then at least
you can help doctors treat it better. That would be a real
boon for mankind."
Cancer is a quasi disease—actually over a hundred diseases
caused by various sorts of mutations inside various cells
in various tissues.
These mutations upregulate some genes, increasing the expression
of metalloproteases for instance, and downregulate others,
shutting off production of receptor proteins. After a certain
number of such events occur, a cancer cell grows out of control,
becoming what is known as a tumor. Tumors threaten the tissues
where they are located. Worse, tumors can metastasize and
migrate through the bloodstream to other tissues—the
reality of malignant carcinoma that claims so many lives every
year.
Immunotherapy—Helping the Body Do What it Should
One approach to cancer therapy that has evolved over the
last few decades is the method of immunotherapy, which aims
to give the immune system a push to start doing what it should
be doing in the first place—killing cancer cells. Immunotherapy
involves helping the T lymphocytes and other cells of the
immune system attack and kill cancer cells, and it is best
at killing small colonies of cancer cells before they grow
into tumors.
One way in which this is accomplished is by presenting the
immune system with tumor-specific antigen. Antigens are markers—proteins
on the surface of a cancer cell, for instance—that are
used by the immune system to distinguish one cell from another.
Immunotherapy entails administering injections of the antigen
and activating the immune system against it.
These injections enable the antigens to be presented by
professional antigen presenting cells, which very effectively
stimulate the immune system. After recognizing the antigens
presented by the antigen presenting cells, the immune cells
become activated and mount an immune defense, selectively
attacking any other cells displaying the antigens—the
cancer cells.
Since cancer cells are originally "self" cells, the trick
is to find some antigen that they display, but which normal
cells in the body do not. Fortunately, the mutations that
cause cancer often cause distinct antigens to appear on the
surface of cancer cells. Sometimes these antigens are overexpressed
on cancer cells, decorating them much more so than normal
cells, and sometimes the antigens are expressed only on cancer
cells. But in any case, they mark the cancer cells, and when
the immune system is stimulated to specifically attack cells
with those antigens, the cancer cells can no longer hide behind
their self faŤade.
"[Cancer] cells masquerade as self," says Reisfeld. "We
do everything we can to take the mask off."
Reisfeld employs a technique called passive immunotherapy,
which involves giving antibodies to a patient that are specific
to tumor cell antigens. The antibodies bind to molecules on
the surface of tumor cells and direct other, cytotoxic immune
cells to them.
One such antibody he discovered is the monoclonal antiganglioside
GD2, which is currently in Phase III clinical trials sponsored
by the National Institutes of Health. GD2 targets the ganglioside
proteins that are expressed on the surface of neuroblastoma
tumors, the second leading cause of childhood cancer and one
for which there is usually a poor prognosis.
"These children have been dying in far too large numbers,"
says Reisfeld, statistics that he hopes GD2 will change.
In the therapy, a recombinant protein is given to a patient
intravenously. The protein is the antibody that is linked
to the cytokine interleukin-2 (IL-2)—a molecule produced
by immune cells that is important in cell growth, adhesion,
and movement. IL-2 is a growth factor for immune cells, like
T cells, macrophages, and natural killer cells. IL-2 binds
to receptors on their surfaces, activates them, and helps
them proliferate.
So the recombinant protein does four things. By virtue of
its GD2 component, it finds the neuroblastoma tumor cells,
binds to them, and attracts immune cells that can kill them.
And significantly, because of the IL-2 component, the recombinant
protein enhances this killing by activating the immune cells
and inducing them to multiply at the site of the tumor.
"GD2 is almost like a guided missile to bring interleukin
to the tumor," says Reisfeld.
Immunotherapy works best at slowing down metastasis in minimal
residual disease, preventing the growth and spread of cancers.
It is not designed to kill big, bulky tumors or address widespread
metastasis. "There we need the surgeon, the radiologist, and
the chemotherapist," says Reisfeld. "They do that."
One patient, he adds, has had great success since starting
the treatment at the age of five. "Now he's 16 and a big boy,"
Reisfeld beams, pointing to a picture on his shelf of a boy,
smiling.
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