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This article by Barbara Fox was prepared for the August 28, 2002 edition of U.S. 1 Newspaper. All rights reserved.
New Attacks on the Big C
Nearly every American family has lost a loved one to
the Big C: cancer. Unlike other diseases, which come in just one or
two virulent versions, cancer can strike dozens of different ways
— through the blood, through a body organ like the breast, lung,
pancreas, colon, or prostate, or even through the skin. And although
researchers have come up with dozens of different ways to prevent
and treat it, to the tune of $60 billion a year, more than one-third
of the people in the United States will be diagnosed with cancer in
their lifetimes. Cancer remains the second leading cause of death
in the United States, exceeded only by heart disease.
Surgery, radiation, and chemotherapy are the traditional ways to stop
cancer cells from growing, but the chemical and radiation poisons
that kill cancer also kill normal cells and cause bad side effects.
News of the latest cancer cures are therefore sure-fire headline grabbers.
aims to cut off the blood supply to starve the cancer cell. Not yet
approved by the FDA.
cancer cell and convince it to commit suicide. Normal cells know when
to stop living, but cancer cells do not. No approvals yet from the
gene to a cancer cell which will alter the properties of the cell.
Or antisense therapy — designing a strand of nucleic acid to block
the tumor’s production of harmful protein. No approvals yet from the
response to proteins found on tumor cells. In cancer, this is a therapeutic
approach to prevent the cancer from spreading. No approvals from the
for use in certain leukemias, such as hairy cell leukemia, and certain
forms of melanoma.
guided missiles, to attach a "bomb" to cancer cells and destroy
them — or to convince the cell to act more like a normal cell.
Two antibody therapies have been approved by the FDA for cancer, one
for lymphoma, the other for breast cancer.
companies and big pharmas keep on plugging away in their labs. On
Wednesday, September 4, at 3 p.m., at the Merrill Lynch conference
center, those who attend the Princeton Chamber trade fair and U.S.
1 technology showcase will have the opportunity to hear about progress
being made by two of those companies. Lisa Drakeman, CEO of Genmab,
and Sidney Pestka, founder of PBL Biomedical Laboratories, will talk
about what their firms are doing to move toward a better cancer cure.
Genmab’s technology, monoclonal antibodies produced by genetically
engineered mice, is one of the trend favorites for 2002. In contrast,
PBL’s technology focuses on a method, interferon research, that had
its heyday 15 years ago but still holds promise today.
Insulin was the first important biological product produced
by genetic engineering, and interferon was the second. Interferons
are among the proteins — some of the human body’s 30,000 to 50,000
different proteins — that regulate the immune system.
In the early 1990s, when drug companies discovered that interferon-based
drugs could successfully treat AIDS, interferons made the headlines.
Now these biotherapeutics are still being used for hepatitis, multiple
sclerosis, AIDS, and some forms of cancer, but interferon research
is seldom touted. Attention has moved on to trendier areas, such as
gene therapy, yet some researchers cling to their interferon work.
They insist this could lead to a much better understanding of how
the cells communicate with each other, which could lead to important
Sidney Pestka remains loyal to the interferon cause. "I believe
that interferon has the potential to treat cancer like no other pharmaceutical
agent I know," says Pestka. "Interferon has been disappointing
as an anti-cancer agent — not because it isn’t powerful enough,
but because it is too powerful. We simply need to figure out how to
harness its potential."
This year Pestka received two significant honors, one of five National
Medals of Technology awarded by President George W. Bush and a Fleet
Bank prize for entrepreneurs that garnered $20,000 split between the
scientist and a charity (U.S. 1, June 26). These honors — one
for scientific exploits, the other for business achievements —
represent Pestka’s unusual status. Not only does he lead an academic
team to do important research on interferons, but he also founded
a profit-making business that is run by his son, Robert.
Rare is the scientist whose work generates a biotech business, let
alone one that is profitable in its early years. Rarer still in the
biotech world is a father-son combination like this.
Pestka Biomedical Laboratories (PBL) is 12 years old, has 25 employees,
and is the world’s largest maker of interferon products for research
laboratory use. It has generated $5 million in profits that have been
injected back into the business. This week CEO Robert Pestka will
triple the company’s space with a move from incubator quarters at
100 Jersey Avenue in New Brunswick to 10,000 square feet in Piscataway.
Sidney Pestka, founder and chief scientific officer, will keep his
12-person laboratory at UMDNJ.
Interferons, produced in the body by white blood cells, are the infection
fighters of your body. When you suffer from headache, fever, muscle
aches, and chills of a viral cold, interferons are at work and the
"symptoms" are interferons’ side effects. For tumors, interferons
can "blow the whistle" by stopping the tumor’s growh, restoring
normal intra-cellular communication, and mustering the immune system’s
apt response. But current delivery methods are way too strong and
cause too many side effects to be useful for any but the most dire
Big pharmas sell nearly $5 billion of interferon drugs annually, say
the Pestkas. Roche holds the patents for 12 forms of alpha interferon
and one beta species, and these patents protect a worldwide market
that includes licenses to the major companies for such ills as Kaposi’s
sarcoma (a tumor associated with AIDS), hepatitis B and C, and multiple
sclerosis. These FDA-approved drugs, prepared as injectable fluids,
are based partly on work that Pestka did at Hoffman LaRoche in the
1980s, and the earliest of these patents has just expired.
In contrast to Roche, PBL makes reagents (chemicals used for research
purposes), and it sells small quantities of these interferon products
in a very pure form — specks in vials, shipped with dry ice, to
laboratory scientists. This income helps to fund PBL’s own drug discovery
In its inventory PBL has 20 types of human interferons and another
15 animal interferons, all sold in nanogram quantities at prices ranging
up to $200. It makes large initial batches of each product and rarely
has to repeat that process. These 100 products are sold in 25 countries
around the world, directly to laboratories and through some of the
larger biochemical companies. PBL’s exclusive products are its assay
kits that enable scientists to easily measure their own interferon
samples without having to create a test themselves.
"We started the way most businesses don’t, with a viable product
line that gives us income, versus raising $.5 million to do some initial
work. Outside investors don’t really know how to look on us,"
says Robert Pestka, who is considering separating the cash cow side
of the business from the new drug side. He wants to clarify the firm’s
financial position in order to attract the investment needed for clinical
Sidney Pestka is the son of a Polish steelworker, tavern
owner, and ingenious inventor. He carries on his father’s trait of
being able to think outside the box. Living first in Brooklyn and
then in Trenton, he graduated from Trenton High and majored in chemistry
at Princeton University, Class of 1957. After graduating from the
University of Pennsylvania medical school he did research at the National
Institutes of Health and the Roche Institute of Molecular Biology.
He was a pioneer in purifying many of the human interferon alpha and
interferon beta species in the late 1970s and early 1980s.
Pestka was department chair at Robert Wood Johnson University Medical
School when the university asked him to start a company. "The
university had suggested that Sid set up a business of his own, mainly
to show that the university was helping to stimulate commercial development,"
says son Robert. Sidney and his wife Joan started the company in their
basement and were employing two part-time scientists when Robert joined
Though Robert’s training is as a civil engineer, he had been working
in his father’s laboratory since ninth grade and entered Princeton
University as a molecular biology major, so he knows the basics of
this technology. "After two years, I had to rebel," says Robert,
telling of his switch to architecture and civil engineering. Graduating
in 1988, he spent four years doing CAD design, construction, and project
management for a Japanese company. When he joined PBL he moved it
out of the basement and into the Rutgers incubator on Jersey Avenue.
Now Robert drives to work from Manhattan, where his wife, Kazumi,
works as a translator and interpreter. He has even had a chance to
dust off his architectural skills. At the time of a telephone interview
he was managing a renovation of the new facilities. "One thing
I can guarantee is our employees will be very happy. Now we have old
laboratory desks scattered around the building and had maxed out our
space. These new facilities are first class," he says.
"We have grown one step beyond the family business," says
Robert. "We have a CFO, a general manager with a PhD who runs
the reagents business, a research director who interfaces with Sid
and runs the drug development program on a day to day business, and
Joan, my mother, who is currently office manager and HR officer."
Interferons were boosted as possible cancer cures in the early 1980s,
and when it became obvious that they weren’t the cure for cancer
there was some skepticism, says Robert Friedman, chairman of the pathology
department at the Uniform Services Medical School in Bethesda, Maryland.
"Interferon may not be the final answer to cancer, but understanding
how it works may lead to some very effective therapies."
"There may be a `lull’ in terms of interferons as a therapy unto
themselves, but interferons have an enormous biological modifier potential.
They alter the biology of the cancer cell and the expression of different
genes in the cancer cell," says Jeffrey Schlom, chief of the laboratory
of tumor immunology and biology at the Center for Cancer Research
at the National Cancer Institute. "Pestka has been leading in
making new interferons that have different properties and making genetically
Sidney Pestka would argue that interferon alpha uses several of the
currently known ways of fighting cancer, including apoptosis, anti-angiogenesis,
and metastatic control. "Interferon has a powerful anti-proliferative
impact that slows the reproduction of tumor cells and destroys metastatic
cancer cells dispersed throughout the body," he says. "As
the most powerful anti-angiogenic agent known, interferon also inhibits
the growth of blood vessels necessary to feed a tumor. Finally, interferon
stimulates apoptosis — the death of tumor cells."
Nevertheless, interferon is most well known for acting as a vaccine
that helps the immune system recognize the diseased cell as a cell
to be attacked. It activates the immune system’s cells — cytotoxic
lymphocytes, natural killer cells, macrophages and dendritic cells
— to attack the cancer cells. What results is not only a direct
attack on the primary tumor, but also the "education" of the
immune system, which is now equipped to find and destroy the metastatic
cells that have escaped from the primary tumor.
Interferon is supposed to be the best late stage treatment for melanoma,
so PBL is working on that. "We ask the question, why didn’t
interferon make the impact that everyone was hoping for. We think
it was because of how it was administered to cancer patients then
and today — too much at once injected in the blood stream, producing
side effects that make patients sick," says Robert.
PBL is also working on a way to inject the interferon directly into
the tumor to stimulate the immune system, as well as on a sustained
release system to reduce the number of injections needed. Patents
have been applied for.
Another new research area is monoclonal radioactive isotopes, funded
by a $1.2 million two-year grant from the NIH. "Our technology
offers a gentle way to label the antibodies with radioisotopes in
a way much more effective than current chemical methods that can deactivate
or denature the antibody and cause toxicity problems," says Robert,
who believes the potential market for this could be as much as $10
Perhaps the most far-reaching of PBL’s technology involves what the
Pestkas call "ultra" interferons. Son Robert says that 10
years ago his father hypothesized that disease cells mutate all of
their proteins, and that this enormous resource of unique, naturally
occurring proteins in cancer cells could be harnessed to treat the
disease. These proteins use the natural pathways of the body’s immune
system. "We looked in cancer cells, starting with interferons,
for new variants of interferons, and we found them, theoretically
an unlimited number. Some of these new proteins, which we call ultra
interferons or ultra human growth hormones, are 15, 25, or even 85
percent better than those currently used," says Robert.
The ultra interferons could be particularly useful to patients who
are getting allergic reactions from the interferons they are currently
using. And because ultra interferon material has been selected to
be effective against a particular disease, less is needed for treatment,
which means the drug is less expensive and has fewer side effects.
Another cost-cutter is that the ultra interferons can get very useful
initial testing on mice.
PBL has already purified 23 ultra interferon alphas. Three were chosen
for further research and preclinical trials, and PBL hopes to partner
with larger companies to develop some of the other ultra interferons
for additional diseases.
"Since my father founded PBL 12 years ago, we have built three,
maybe four technology platforms that have great potential," says
Robert Pestka. "He developed interferon for human use. He bridged
the gap between discovering interferon and making it practical to
treat people in large groups. Many of his groundbreaking discoveries
came about because he went against the prevailing thinking of the
Sidney Pestka agrees. "I have been doing that all my life. You
have to do what you think makes sense. Now my early work is being
listed as dogma. No one was interested in my work on interferon at
the Roche Institute. I went ahead anyway, and it made an impact. There
have been advances by other companies, but our goal is to make a real
dent in cancer."
"Cancer research has gone through all sorts of fads," says
Sidney. "We had the genomic fad, and right now we have the proteomic
fad. They are very important but I don’t think they should be oversold.
I don’t want to downplay proteomics and genomics because I use them
— they can add additional knowledge about how interferons work.
Just studying genomics and proteomics is not going to lead us to a
cancer cure. To understand the biology of cancer, you have to integrate
Piscataway 08854. Robert Pestka, president and CEO. 732-777-9123;
fax, 732-777-9141. Www.pblbio.com
concentrate on important problems than on trivial ones, and the rewards
are far greater with the former.
collaborations as a key to much of his success.
interview with Sidney Pestka, who was then president of the International
Society for Interferon and Cytokine Research.
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