textfiles/bbs/KEELYNET/BIOLOGY/cancbomb.asc

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|  File Name      : CANCBOMB.ASC     |  Online Date     :  01/15/96          |
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                 Smart Bombs Aimed At Cancer Cell Blood Supply

Imagine a cure for cancer that recruits the body's own first line of defense -
its antibodies - to seek and destroy tumors, without causing any of the nasty
side effects of chemotherapy. That scenario describes a brilliant new
technique now being developed at the University of Massachusetts Amherst.

About 20 years ago, UMass microbiologist Bruce Jacobson began some basic
research that involved laminating slime mold with a plastic coating that
contained ingredients commonly found in antiperspirant and floor polish. The
purpose of his laminating technique was to peel away the outer membranes on
individual cells of slime mold in order to identify the specific proteins
located there.

Today Jacobson, using this same laminating concept to identify proteins in
blood vessel cells of malignant tumors, is on the verge of creating a magic
bullet. By producing antibodies to those identified proteins, Jacobson hopes
to make biological agents that can home in, like heat-seeking missiles, on the
blood vessels in a cancerous growth and thereby kill the cancer.  Researchers
in the early 1970s posed the theory that one sure way to control a tumor was
to destroy its blood vessels.

"All cells in the body have to be within a millimeter or two of a capillary,"
explains Jacobson. "Otherwise the tissue doesn't receive nutrients, and it
can't get rid of wastes."

Tumor cells are no exception. Like invading armies in the field, tumors must
keep supply lines open and have to dispose of waste products. Attacking such
supply lines requires finding a kind of smart bomb that can kill blood vessels
within the tumor but leave arteries in nearby healthy tissue unharmed.
Jacobson's method targets specific proteins which are unique to endothelial
cells forming the linings of blood vessels in malignant tumors, by using the
proteins' own antibodies.

But imagine peeling a grape the size of a single cell! In effect, Jacobson and
his team had to figure a way to do just that in order to examine the proteins
in the cell's membrane.  The answer lies in an innovative technique Jacobson
had developed in the mid-1970s for separating the membranes away from slime-
mold cells. The trick is to coat each cell with something heavy and magnetic
that allows the membrane to be skinned.

Jacobson's coating is a relatively heavy mixture of plastic, glass beads
(called colloidal silica, found in floor polish) and an aluminum compound
contained in antiperspirants. The final result is a charged sandwich of
membrane and glass and plastic, which encases each cell like a sheet of
lamination.  When Jacobson homogenizes cells prepared in this way and places
the resulting puree in solution, the heavier pieces of treated membrane settle
to the bottom like grains of sugar. Then he can examine the separated
membranes, using standard techniques, and identify the associated
proteins.

In the late 1980s, Jacobson realized that by using his laminating technique on
the endothelial cells lining the blood vessels in cancer tumors, he could
identify proteins specific to that location in those tumors. Then he could
create antibodies to those proteins that would seek out and lock onto tumor
blood vessels only.  One problem with this approach was that Jacobson had to
figure out a way to apply his laminating technique in vivo. The procedure he
developed with lab animals demonstrates a shrewd variation on his earlier
technique with mold.

First, the team induces tumors in the animal. After tumors are established,
the team anesthetizes the animal, using humane methods suggested by the
National Institutes of Health. The team next forces a plain buffer liquid into
arteries and drains the blood. At this point, the animal is brain dead, but
its body functions are sustained on life support.

"After flushing out the blood," says Jacobson, "we flush in colloidal silica.
You can visualize that as it's flushing through, it coats all the surfaces of
the endothelial cells with this positively charged silica. We then flush in
the negatively charged plastic in a water-soluble solution."

Using that technique, Jacobson laminates all the blood vessel linings in the
body of the animal, including, most importantly, those within tumors, which he
then surgically removes.  The Jacobson team is currently identifying the
distinct proteins it has found in endothelial cell membranes from tumors. Once
an effective antibody has been produced for selected target proteins, the team
will have at least two alternatives for killing a cancer tumor.

Injected into a person suffering from a cancer tumor, these antibodies will
bind to numerous endothelial cells within the growth, causing massive blood
clotting. Scientists call this mechanism a "cascade." Or there's an
alternative. The team can link a commercially-available toxin to the
antibodies it has created and, in effect, selectively poison the tumor.

Jacobson predicts that the first testing on human beings will begin in two to
four years, depending on funding, which he is seeking from commercial biotech
companies. At that point, the magic bullet Jacobson is seeking will be loaded,
aimed and ready to fire.
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