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Immunotherapy Cancer Treatment
John W. Park, MD
Christopher C. Benz, MD
Reprinted with Permission from Supportive Cancer Careby
E.H. Rosenbaum, MD and I.R. Rosenbaum, Sourcebooks, Naperville,
IL, 2001
Interferons and Other Cytokines
Monoclonal Antibodies
Cancer Vaccines
The concept of immunotherapy is based
on the body's natural defense system, which protects us
against a variety of diseases. Although we are less aware
of it, the immune system also works to aid our recovery
from many illnesses.
For many years, physicians believed that the immune system
was effective only in combating infectious diseases caused
by such invading agents as bacteria and viruses.
More recently, we have learned that the immune system may
play a central role in protecting the body against cancer
and in combating cancer that has already developed.
This latter role is not well understood, but there is evidence
that in many cancer patients the immune system slows down
the growth and spread of tumors. The body's ability to develop
an immune reaction to tumors may help determine which patients
are cured of cancer using conventional therapies, including
surgery, radiation and drugs.
One immediate goal of research in cancer immunology is the
development of methods to harness and enhance the body's
natural tendency to defend itself against malignant tumors.
Immunotherapy represents a new and powerful weapon in the
arsenal of anticancer treatments.
Immunotherapy seems to offer great promise as a new dimension
in cancer treatment, but it is still very much in its infancy.
Immunotherapies involving certain cytokines and antibodies
have now become part of standard cancer treatment. Other
examples of immunotherapy remain experimental. Although
many clinical trials of new forms of immunotherapy are in
progress, an enormous amount of research remains to be done
before the findings can be widely applied.
Immunotherapy of cancer began about one hundred years ago
when Dr. William Coley, at the Sloan-Kettering Institute,
showed that he could control the growth of come cancers
and cure a few advanced cancers with injections of a mixed
vaccine of streptococcal and staphylococcal bacteria known
as Coley's toxin. The tuberculosis vaccine, Bacillus Calmette-Guerin
(BCG), developed in 1922, is known to stimulate the immune
system and is now used to treat bladder cancers.
Many years of research have finally produced the first successful
examples of immunotherapies for cancer.
Sometimes referred to as biological response modifiers or
as biological therapies, these new treatments-such as interferons
and other cytokines, monoclonal antibodies, and vaccine
therapies-have generated renewed interest and research activity
in immunology.
Interferons and Other Cytokines
Interferons belong to a group of proteins known as cytokines.
They are produced naturally by white blood cells in the
body (or in the laboratory) in response to infection, inflammation,
or stimulation. They have been used as a treatment for certain
viral diseases, including hepatitis B.
Interferon-alpha was one of the first cytokines to show
an antitumor effect, and it is able to slow tumor growth
directly, as well as help to activate the immune system.
Interferon-alpha has been approved by the FDA and is now
commonly used for the treatment of a number of cancers,
including multiple myeloma, chronic myelogenous leukemia,
hairy cell leukemia, and malignant melanoma. Interferon-beta
and interferon-gamma are other types of interferons that
have been investigated.
Other cytokines with antitumor activity include the interleukins
(e.g., IL-2) and tumor necrosis factor. IL-2 is frequently
used to treat kindey cancer and melanoma.
Some of the problems with these cytokines, including many
of the interferons and interleukins, are their side effects,
which include malaise and flu-like syndromes. When given
at a high dose, the side effets can be greatly magnified.
Monoclonal Antibodies
Another important biological therapy involves antibodies
against cancer cells or cancer-associated targets. Monoclonal
antibodies are artificial antibodies against a particular
target (the "antigen") and are produced in the
laboratory. The original method involved hybridoma cells
(a fusion of two different types of cells) that acted as
factories of antibody production. A major advance in this
field was the ability to convert these antibodies, which
originally were made from mouse hybridomas, to "humanized"
antibodies tha more closely resemble our natural antibodies.
Even newer techniques can be used to generate human antibodies
from genetically engineered mice or bacteria containing
human antibody genes. Monoclonal antibodies have been widely
used in scientific studies of cancer, as well as in cancer
diagnosis.
As therapy for cancer, monoclonal antibodies can be injected
into patients to seek out the cancer cells, potentially
leading to disruption of cancer cell activities or to enhancement
of the immune response againast the cancer. This strategy
has been of great interest since the original invention
of monoclonal antibodies in the 1970s. After many years
of clinical testing, researchers have proven that improved
monoclonal antibodies can be used effectively to help treat
certain cancers. An antibody called rituximab (Rituxan)
can be useful in the treatment of non-Hodgkin's lymphoma,
while trastuzumab (Herceptin) is useful against certain
breast cancers. Other new monoclonal antibodies are undergoing
active testing.
Researchers also are studying ways of linking cytotoxic
drugs, toxins, or radioisotopes to monoclonal antibodies
to enhance their effectiveness against cancer cells. In
this case, the antibodies would function as a targeted delivery
mechanism; the result would be like a "guided missile,
" capable of seeking out a specific target-a cancer
cell.
Cancer Vaccines
As described above, biological therapy or immunotherapy
is now considered a fourth modality of cancer treatment,
and examples such as interferon and monoclonal antibodies
have become part of standard cancer treatment. Many types
of immunotherapy, such as cancer vaccines, remain experimental.
Experimental therapies in general are also discussed in
the next section.
Vaccines have revolutionized public health by preventing
the development of many important infectious diseases, including
polio, small pox, and diphtheria. It has been much more
difficult to develop effective vaccines to prevent cancer,
or to treat patients who already have cancer.
Attempts to develop such cancer vaccines, despite many decades
of experimental work, have yet to yield proven results.
In spite of this, a notable increase in interest has been
generated by recent advances in the areas of immunology
and cancer biology, which have led to more sophisticated
and promising vaccine strategies than those previously available.
Cancer vaccines typically consist of a source of cancer-associated
material (antigen), along with other components, to further
stimulate the immune response against the antigen. The challenge
has been to find better antigens, as well as to package
the antigen in such a way as to enhance the patient's immune
system to fight cancer cells that have the antigen.
Increasingly, cancer vaccines have been shown to be capable
of improving the immune response against particular antigens.
The result of this immunologic effect is not always sufficient
to reverse the progression of cancer.
However, cancer vaccines have been generally well tolerated,
and they may provide useful anticancer effects in some situations.
For example, in malignant lymphoma, a number of laboratory
studies have indicated that vaccination using lymphoma-associated
proteins called "idiotype" can stimulate the immune
systems of mice sufficiently to help them resist the development
of lymphomas.
In clinical trials, idiotype vaccines continue to be tested
and have been associated with indications of clinical benefit
in some lymphoma patients. In malignant melanoma, a wide
variety of vaccine strategies have been introduced into
clinical trials, and some have been found to stimulate the
immune response against the cancer.
Cancer vaccines continue to be evaluated in these diseases
as well as most other cancer types. The many new strategies
for vaccine construction and immune stimulation may lead
to the emergence of clinically useful cancer vaccines. An
example of one exciting new approach being tested in melanoma
and other cancers is the use of dendritic cell vaccines.
Dendritic cells help to "turn on" the immune response.
http://www.cancersupportivecare.com/
immunotherapy.html
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