At the Bio 98 International Biotechnology Meeting and Exhibition, three
biotechnology companies discussed their efforts to develop anticancer
vaccines.
Imagine attending a party where the "party police" are either
overwhelmed by the troublemakers or do not even recognize them. Such is the
relationship between the immune system, which is well known for fighting
infectious diseases, and cancer, against which it struggles. However, over
the past fifteen years, research about how the major histocompatibility
complex (MHC) molecules enable the immune system to detect its targets has
led to promising advances in anticancer vaccines.
At the Bio 98 International Biotechnology Meeting and Exhibition, held June
14-18 in New York City, three biotechnology companies discussed their
efforts to develop anticancer vaccines, an endeavor that focuses on
identifying "cancer" antigens and delivering them in a way that
will stimulate the immune system. The twelfth annual meeting of its kind,
the conference was, according to a participant, ""probably the first
time so many suits and nerds were together in the same place," at least
outside of a computer-related conference. While no cancer vaccines are yet
on the market, the companies reported several studies that are in the
clinical phase. As Mark McDade, chief financial officer of Corixa Corporation said, "Now there
are quite a few cancer vaccine clinical trials at the phase II stage, which
means we'll be seeing successes over the next few years."
Using the immune system to fight cancer is not novel. "At the turn of
the century, experiments were performed on rats where it became evident that
the immune system could 'shrink' tumors," said Howard Kaufman,
assistant professor at the Albert
Einstein College of Medicine. Scientists injected tumor-ridden mice with
bacterial toxins that, surprisingly, caused tumor regression. Although the
toxins had nothing to do with the cancer, they appeared to activate the
immune system, which in turn attacked the tumors. From this grew the idea
that because the immune system is not active enough in individuals with
early cancer, it does not naturally eliminate tumors.
Are there examples in which the immune system, unaided by a vaccine, fights
cancer? Since a non-progressing tumor is unlikely to be noticed by
physicians, it is hard to say. However, Kaufman said that physicians have
noted cases in which certain types of tumors, especially melanomas, became
smaller or disappeared on their own - perhaps positive examples of immune
system function. Researchers now believe that the immune system may be
ineffective against particular cancers because it is overwhelmed by the
tumor, or it can't recognize tumors not displaying unique antigens, or is
somehow tricked by the tumor into inactivity.
All three companies presenting at the conference (Argonex, Corixa, and Dendreon) were focusing on stimulating
the T-cell-mediated responses of the immune system. According to David Urdal,
chief scientific and operations officer of Dendreon, "There are many examples where an antibody response alone may be inadequate. Most researchers would agree that the stimulation of a robust cell-mediated immune response is likely to be of even greater benefit. Conditions under which both an antibody and T-cell response are stimulated might be the best of all."
That is not to say that antibody-based cancer therapy is a waste of time. Explained Urdal,
"The work, for example, of Ronald Levy demonstrated conditions under which an antibody response to B cell lymphoma in fact can be of clinical benefit."
Indeed, the only therapy to have won FDA approval is rituxan, a
monoclonal antibody developed by IDEC Pharmaceticals,
used to treat non-Hodgkin's lymphoma. Herceptin, a monoclonal antibody
developed by Genentech against a
breast cancer antigen, is still awaiting FDA approval. However, these
approaches are not considered vaccines
because they are short-term therapies, relying on directly administering the
antibody rather than stimulating an immune response.
According to
Aris Persidis, vice president of business development of Argonex, "There are approximately ten companies focusing
on anticancer vaccines designed to stimulate a T-cell response."
Companies such as Argonex are focused on the front end, discovering antigens
that may distinguish a cancer cell from a normal cell.
"Since only certain types of tumors such as melanomas express unique
antigens, Dendreon's efforts are aimed at figuring out what we can do to
trick the immune system so that any tumor is seen as foreign,"
explained Urdal. He added that by loading antigen onto dendritic cells, which
are specialized to present antigen to the immune system, they are able to
spark an immune response against an antigen that normally does not evoke a
defense.
Vaccine approaches that use antigens unique to specific tissues, rather than
to tumor cells, usually focus on cancers where the organ is nonessential,
such as in prostate cancer, in case an immune response is mounted to the
organ itself. However, since tumor cells usually overexpress antigens, the
immune response generated by the vaccine largely focuses on the
tumor.
According to Kaufman, there is no consensus yet on the best antigen delivery
system. Corixa Corporation has designed a way to polymerize the antigen into
a microsphere, which they believe is the most effective way to stimulate
both a cytotoxic T cell and a helper T cell response.
The main advantage of a vaccine approach to cancer therapy is the absence of
side effects. "What's really hopeful is that the process is extremely
safe and well tolerated; one is not administering poisons as one does in
chemotherapy," said Urdal. But the vaccines, once approved, could only
be used as an adjunct to conventional therapy. The tumor would still have to
be removed surgically, since it is too large a mass to be attacked by immune
cells. The vaccine would stimulate the body, destroying any
remaining cancerous cells. The goal of a vaccine would be to prevent a
recurrence of cancer.
One potential hurdle to approving antitumor vaccines is that the efficacy
data may not be strong because vaccine tests are not performed under optimal
conditions. Patient trials are possible only at a late stage of disease,
when no other treatment options are available. But vaccines are more likely
to work when an immune system is robust, in the earlier stages of cancer.
Optimistically, if vaccines prove to be beneficial at late stages, they may
prove even more effective when used earlier. As Urdal said, "The hope
is to use the vaccines when the tumor mass is the smallest, either right
after surgery as an anti-metastatic therapy, or at an early stage where one
has identified a potential malignancy."
Anjani Shah is a freelance science/medical writer.
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BioSpace - the latest news about the
biotechnology and pharmaceutical
industry, including updates on particular products and what stage trials
they are in.
Coley's Toxins/Issel's Fever Therapy - gives a brief history behind the
early use of immunotherapy for cancer patients by William Coley. For more
information on the connection between Coley, the Rockefellers, and cancer
research, see chapter one of A Commotion in the Blood by Stephen Hall.
Immune Therapy for Cancer -
maintained by the University of Washington Medical Center, this site
provides a basic introduction to cancer immunotherapy.
Cancer Research Institute -
cofounded by William Coley's daughter, Helen Coley Nauts, this
organization is devoted to furthering advances in cancer immunotherapy.
At the Bio 98 International Biotechnology Meeting and Exhibition, held June
14-18 in New York City, three biotechnology companies discussed their
efforts to develop anticancer vaccines, an endeavor that focuses on
identifying "cancer" antigens and delivering them in a way that
will stimulate the immune system. The twelfth annual meeting of its kind,
the conference was, according to a participant, ""probably the first
time so many suits and nerds were together in the same place," at least
outside of a computer-related conference. While no cancer vaccines are yet
on the market, the companies reported several studies that are in the
clinical phase. As Mark McDade, chief financial officer of Corixa Corporation said, "Now there
are quite a few cancer vaccine clinical trials at the phase II stage, which
means we'll be seeing successes over the next few years."
Using the immune system to fight cancer is not novel. "At the turn of
the century, experiments were performed on rats where it became evident that
the immune system could 'shrink' tumors," said Howard Kaufman,
assistant professor at the 
All three companies presenting at the conference (
According to
Aris Persidis, vice president of business development of Argonex, "There are approximately ten companies focusing
on anticancer vaccines designed to stimulate a T-cell response."
Companies such as Argonex are focused on the front end, discovering antigens
that may distinguish a cancer cell from a normal cell.
"Since only certain types of tumors such as melanomas express unique
antigens, Dendreon's efforts are aimed at figuring out what we can do to
trick the immune system so that any tumor is seen as foreign,"
explained Urdal. He added that by loading antigen onto dendritic cells, which
are specialized to present antigen to the immune system, they are able to
spark an immune response against an antigen that normally does not evoke a
defense.
Vaccine approaches that use antigens unique to specific tissues, rather than
to tumor cells, usually focus on cancers where the organ is nonessential,
such as in prostate cancer, in case an immune response is mounted to the
organ itself. However, since tumor cells usually overexpress antigens, the
immune response generated by the vaccine largely focuses on the
tumor.
The main advantage of a vaccine approach to cancer therapy is the absence of
side effects. "What's really hopeful is that the process is extremely
safe and well tolerated; one is not administering poisons as one does in
chemotherapy," said Urdal. But the vaccines, once approved, could only
be used as an adjunct to conventional therapy. The tumor would still have to
be removed surgically, since it is too large a mass to be attacked by immune
cells. The vaccine would stimulate the body, destroying any
remaining cancerous cells. The goal of a vaccine would be to prevent a
recurrence of cancer.
One potential hurdle to approving antitumor vaccines is that the efficacy
data may not be strong because vaccine tests are not performed under optimal
conditions. Patient trials are possible only at a late stage of disease,
when no other treatment options are available. But vaccines are more likely
to work when an immune system is robust, in the earlier stages of cancer.
Optimistically, if vaccines prove to be beneficial at late stages, they may
prove even more effective when used earlier. As Urdal said, "The hope
is to use the vaccines when the tumor mass is the smallest, either right
after surgery as an anti-metastatic therapy, or at an early stage where one
has identified a potential malignancy."
