Antigenics again,
forbes.com
Vaccines are the hottest new weapon in the war
against cancer. Antigenics has found a way to
customize them.
In search of antigens
By Zina Moukheiber, in Forbes
MICHAEL MILKEN, himself a victim of
prostate cancer, has spent heavily and given freely
of his time to promote cancer treatment. At a
gathering of 120 scientists in September, Milken
introduced Garo Armen as "the man who may
cure cancer." Sighed Armen: "We all hope."
A 44-year-old chemist-turned-financier, Armen is
chairman of Antigenics Llc., a
Manhattan-headquartered biotech startup
working on vaccines that attack tumors. He also
heads Armen Partners L.P., a health care
investment fund with $80 million under
management. Like Milken, Armen has a lot at
stake in the fight against cancer: His mother died
painfully of breast cancer.
Many cancer specialists see vaccines as a
plausible alternative to drug therapy. These
vaccines resemble those used against smallpox or
polio in that they use a piece of the target-there
a virus, here a cancer cell-to boost the immune
system's ability to find and attack those targets.
But the cancer vaccines differ in that they're
meant to fight the disease rather than prevent it.
The problem with cancer cells is that they are not
foreign invaders, but fifth-column traitors. The
body can't tell them from healthy cells. So the
trick is to find the slightest trait specific to cancer
cells and to train the body to recognize it. Such
traits-whether of viruses, ragweed pollen or
cancer-are called antigens.
Antigens stick out from cells like molecular
signposts, saying "kick me" to the immune
system's soldiers. For some reason, the antigens
on tumor cells don't grab the soldiers' attention
strongly enough. So the scientists
extract the antigens from tumors,
purify them, multiply them and
then inject them into the patient. If
all goes well, the beefed-up
antigens will then spark an
immune assault on the tumor.
Several biotech and pharmaceutical companies
are trying to identify tumor-specific antigens. New
York-based ImClone Systems, for instance, is
targeting lung cancer antigens. Genzyme
Molecular Oncology, a division of Genzyme
General, of Cambridge, Mass., says it has
isolated melanoma antigens.
Out of tens of thousands of proteins in a cancer
cell, less than one in a thousand may become a
cancer antigen. Finding the antigens is like
searching a beach for a particular grain of sand.
One strategy is to look not for the antigen itself
but for certain helper proteins, called chaperones,
that bring the antigen to the attention of the
immune system. Antigenics focuses on a class of
chaperones known as heat-shock proteins
(HSP), first studied in this regard by Pramod
Srivastava, a cofounder of Antigenics and a
cancer specialist at the University of Connecticut
School of Medicine, in Farmington.
Heat-shock proteins have been known to repair
damaged proteins and escort those beyond repair
to the body's junkyards. Srivastava discovered
that three, possibly four, types of HSP go further,
prompting immune cells to attack cancerous cells.
"We're allowing the HSPs to seek them
[antigens] out for us," he says.
Here's how it works. The surgeon removes
tumors from a patient, puts them on dry ice and
sends them overnight to the Antigenics laboratory
in Framingham, Mass., where the heat shock
proteins are extracted, processed and sent back.
Fifteen days later, after the patient has recovered
a bit from the operation, he gets the vaccine.
The procedure must be customized in this fashion
because each patient's cancer is unique, with a
unique set of mutations, Srivastava says.
The vaccine has caused tumors to regress in mice,
and a trial in 14 seriously ill humans stimulated
immune response without harmful side effects. No
cures were effected, however, perhaps because
the patients were so sick. They had to be to
qualify for the experimental treatment. Antigenics
started the next round of clinical trials in June at
New York's Memorial Sloan-Kettering Cancer
Center. They will start this month at M.D.
Anderson Cancer Center in Houston.
Armen estimates that treatment with his vaccines
might cost between $10,000 and $15,000 per
treatment. Still, that's no more than standard
chemotherapy costs.
Could Milken be right about Armen? Physicians
like to cite a rule: Don't use the words "cure" and
"cancer" in the same sentence. In this field a
treatment counts as a success if it merely
complements existing weapons, perhaps by
offering options to patients who cannot tolerate
chemotherapy. It seems that Antigenics' vaccine
has a fair chance of going at least that far. |
