- What is biological therapy?
Biological therapy (sometimes called immunotherapy,
biotherapy,
or biological
response modifier therapy) is a relatively new addition to the family
of cancer treatments that also includes surgery,
chemotherapy,
and radiation
therapy. Biological therapies use the body's immune system, either directly
or indirectly, to fight cancer or to lessen the side effects that may be caused
by some cancer treatments.
- What is the immune system and what are its components?
The immune system is a complex network of cells
and organs
that work together to defend the body against attacks by “foreign”
or “non-self” invaders. This network is one of the body's main
defenses against infection
and disease. The immune system works against diseases, including cancer, in
a variety of ways. For example, the immune system may recognize the difference
between healthy cells and cancer cells in the body and works to eliminate
cancerous cells. However, the immune system does not always recognize cancer cells as
“foreign.” Also, cancer may develop when the immune system breaks
down or does not function adequately. Biological therapies are designed to
repair, stimulate, or enhance the immune system's responses.
Immune system cells include the following:
-
Lymphocytes
are a type of white
blood cell found in the blood
and many other parts of the body. Types of lymphocytes include B
cells, T
cells, and Natural
Killer cells.
B cells (B
lymphocytes) mature into plasma
cells that secrete proteins
called antibodies (immunoglobulins). Antibodies recognize and attach to foreign substances
known as antigens,
fitting together much the way a key fits a lock. Each type of B cell
makes one specific antibody, which recognizes one specific antigen.
T cells (T lymphocytes) work primarily by producing
proteins called cytokines.
Cytokines allow immune system cells to communicate with each other and
include lymphokines, interferons, interleukins, and colony-stimulating
factors. Some T cells, called cytotoxic
T cells, release pore-forming proteins that directly attack infected,
foreign, or cancerous cells. Other T cells, called helper
T cells, regulate the immune response by releasing cytokines to
signal other immune system defenders.
Natural Killer cells (NK cells) produce powerful
cytokines and pore-forming proteins that bind to and kill many foreign
invaders, infected cells, and tumor cells. Unlike cytotoxic T cells,
they are poised to attack quickly, upon their first encounter with their
targets.
-
Phagocytes are white blood cells that can swallow
and digest microscopic
organisms and particles in a process known as phagocytosis. There are
several types of phagocytes, including monocytes, which
circulate in the blood, and macrophages,
which are located in tissues
throughout the body.
- What are biological response modifiers, and how can they
be used to treat cancer?
Some antibodies, cytokines, and other immune system substances can be produced
in the laboratory for use in cancer treatment. These substances are often
called biological response modifiers (BRMs). They alter the interaction between
the body's immune defenses and cancer cells to boost, direct, or restore the
body's ability to fight the disease. BRMs include interferons, interleukins,
colony-stimulating factors, monoclonal antibodies, vaccines, gene therapy,
and nonspecific immunomodulating agents. Each of these BRMs is described in
Questions 4 to 10.
Researchers continue to discover new BRMs, to learn more about how they function,
and to develop ways to use them in cancer therapy.
Biological therapies may be used to:
- Stop, control, or suppress processes that permit cancer growth.
- Make cancer cells more recognizable and, therefore, more susceptible to
destruction by the immune system.
- Boost the killing power of immune system cells, such as T cells, NK cells,
and macrophages.
- Alter the growth patterns of cancer cells to promote behavior like that
of healthy cells.
- Block or reverse the process that changes a normal cell or a precancerous
cell into a cancerous cell.
- Enhance the body's ability to repair or replace normal cells damaged or
destroyed by other forms of cancer treatment, such as chemotherapy or radiation.
- Prevent cancer cells from spreading to other parts of the body.
Some BRMs are a standard part of treatment for certain types of cancer, while
others are being studied in clinical
trials (research studies). BRMs are being used alone or in combination
with each other. They are also being used with other treatments, such as radiation
therapy and chemotherapy.
- What are interferons?
Interferons (IFNs) are types of cytokines that occur naturally in the body.
They were the first cytokines produced in the laboratory for use as BRMs.
There are three major types of interferons—interferon
alpha, interferon
beta, and interferon
gamma; interferon alpha is the type most widely used in cancer treatment.
Researchers have found that interferons can improve the way a cancer patient's
immune system acts against cancer cells. In addition, interferons may act
directly on cancer cells by slowing their growth or promoting their development
into cells with more normal behavior. Researchers believe that some interferons
may also stimulate NK cells, T cells, and macrophages, boosting the immune
system's anticancer function.
The U.S. Food and Drug Administration (FDA) has approved the use of interferon
alpha for the treatment of certain types of cancer, including hairy
cell leukemia, melanoma,
chronic
myeloid leukemia, and AIDS-related
Kaposi's sarcoma.
Studies have shown that interferon alpha may also be effective in treating
other cancers such as kidney
cancer and non-Hodgkin lymphoma.
Researchers are exploring combinations of interferon alpha and other BRMs
or chemotherapy in clinical trials to treat a number of cancers.
- What are interleukins?
Like interferons, interleukins (ILs) are cytokines that occur naturally in
the body and can be made in the laboratory. Many interleukins have been identified;
interleukin-2
(IL2 or aldesleukin)
has been the most widely studied in cancer treatment. IL2 stimulates
the growth and activity of many immune cells, such as lymphocytes, that can
destroy cancer cells. The FDA has approved IL2 for the treatment of
metastatic
kidney cancer and metastatic melanoma.
Researchers continue to study the benefits of interleukins to treat a number
of other cancers, including leukemia,
lymphoma, and brain, colorectal,
ovarian,
breast,
and prostate
cancers.
- What are colony-stimulating factors?
Colony-stimulating factors (CSFs) (sometimes called hematopoietic
growth factors) usually do not directly affect tumor cells; rather, they
encourage bone
marrow stem
cells to divide and develop into white blood cells, platelets,
and red
blood cells. Bone marrow is critical to the body's immune system because
it is the source of all blood cells.
Stimulation of the immune system by CSFs may benefit patients undergoing
cancer treatment. Because anticancer drugs
can damage the body's ability to make white blood cells, red blood cells,
and platelets, patients receiving anticancer drugs have an increased risk
of developing infections, becoming anemic,
and bleeding more easily. By using CSFs to stimulate blood cell production,
doctors can increase the doses
of anticancer drugs without increasing the risk of infection or the need for
transfusion
with blood products. As a result, researchers have found CSFs particularly
useful when combined with high-dose
chemotherapy.
Some examples of CSFs and their use in cancer therapy are as follows:
- GCSF
(filgrastim)
and GMCSF (sargramostim)
can increase the number of white blood cells, thereby reducing
the risk of infection in patients receiving chemotherapy. GCSF and
GMCSF can also stimulate the production of stem cells in preparation
for stem cell or bone
marrow transplants.
- Erythropoietin
(epoetin) can increase the number of red blood cells and reduce
the need for red blood cell transfusions in patients receiving chemotherapy.
- Interleukin-11
(oprelvekin) helps the body make platelets and can reduce the
need for platelet transfusions in patients receiving chemotherapy.
Researchers are studying CSFs in clinical trials to treat a large variety
of cancers, including lymphoma, leukemia, multiple
myeloma, melanoma, and cancers of the brain, lung,
esophagus,
breast, uterus,
ovary,
prostate, kidney,
colon,
and rectum.
- What are monoclonal antibodies?
Researchers are evaluating the effectiveness of certain antibodies made in
the laboratory called monoclonal antibodies (MOABs or MoABs). These antibodies
are produced by a single type of cell and are specific for a particular antigen.
Researchers are examining ways to create MOABs specific to the antigens found
on the surface of various cancer cells.
To create MOABs , scientists first inject human cancer cells into mice. In
response,
the mouse immune system makes antibodies against these cancer cells. The scientists
then remove the mouse plasma cells that produce antibodies, and fuse them
with laboratory-grown cells to create “hybrid” cells called hybridomas.
Hybridomas can indefinitely produce large quantities of these pure antibodies,
or MOABs.
MOABs may be used in cancer treatment in a number of ways:
-
MOABs that react with specific types of cancer may enhance a patient's
immune response to the cancer.
-
MOABs can be programmed to act against cell growth
factors, thus interfering with the growth of cancer cells.
-
MOABs may be linked to anticancer drugs, radioisotopes
(radioactive
substances), other BRMs, or other toxins.
When the antibodies latch onto cancer cells, they deliver these poisons
directly to the tumor, helping to destroy it.
MOABs carrying radioisotopes may also prove useful in diagnosing
certain cancers, such as colorectal, ovarian, and prostate.
Rituxan® (rituximab)
and Herceptin®
(trastuzumab)
are examples of MOABs that have been approved by the FDA. Rituxan
is used for the treatment of non-Hodgkin lymphoma. Herceptin is used to treat
metastatic breast
cancer in patients with tumors
that produce excess amounts of a protein called HER2. (More information
about Herceptin is available in the National
Cancer Institute (NCI) fact sheet Herceptin® (Trastuzumab):
Questions and Answers, which can be found at http://www.cancer.gov/cancertopics/factsheet/Therapy/herceptin
on the Internet.) In clinical trials, researchers are testing MOABs to treat
lymphoma, leukemia, melanoma, and cancers of the brain, breast, lung, kidney,
colon, rectum, ovary, prostate, and other areas.
- What are cancer vaccines?
Cancer vaccines are another form of biological therapy currently under study.
Vaccines for infectious diseases, such as measles, mumps, and tetanus, are
injected
into a person before the disease develops. These vaccines are effective because
they expose the body's immune cells to weakened forms of antigens that are
present on the surface of the infectious agent. This exposure causes the immune
system to increase production of plasma cells that make antibodies specific
to the infectious agent. The immune system also increases production of T
cells that recognize the infectious agent. These activated immune cells remember
the exposure, so that the next time the agent enters the body, the immune
system is already prepared to respond and stop the infection.
Researchers are developing vaccines that may encourage the patient's immune
system to recognize cancer cells. Cancer vaccines are designed to treat existing
cancers (therapeutic
vaccines) or to prevent the development of cancer (prophylactic
vaccines). Therapeutic vaccines are injected in a person after cancer is diagnosed.
These vaccines may stop the growth of existing tumors, prevent cancer from
recurring,
or eliminate cancer cells not killed by prior treatments. Cancer vaccines
given when the tumor is small may be able to eradicate the cancer. On the
other hand, prophylactic vaccines are given to healthy individuals before
cancer develops. These vaccines are designed to stimulate the immune system
to attack viruses
that can cause cancer. By targeting these cancer-causing viruses, doctors
hope to prevent the development of certain cancers.
Early cancer
vaccine clinical trials involved mainly patients with melanoma. Therapeutic
vaccines are also being studied in the treatment of many other types of cancer,
including lymphoma, leukemia, and cancers of the brain, breast, lung, kidney,
ovary, prostate, pancreas,
colon, and rectum. Researchers are also studying prophylactic vaccines to
prevent cancers of the cervix
and liver.
Moreover, scientists are investigating ways that cancer vaccines can be used
in combination with other BRMs.
- What is gene therapy?
Gene therapy is an experimental
treatment that involves introducing genetic
material into a person's cells to fight disease. Researchers are studying
gene therapy methods that can improve a patient's immune response to cancer.
For example, a gene
may be inserted into an immune cell to enhance its ability to recognize and
attack cancer cells. In another approach, scientists inject cancer cells with
genes that cause the cancer cells to produce cytokines and stimulate the immune
system. A number of clinical trials are currently studying gene therapy and
its potential application to the biological
treatment of cancer. (More information about gene therapy is available in
the NCI fact sheet Gene Therapy for Cancer: Questions and Answers, which
can be found at http://www.cancer.gov/cancertopics/factsheet/Therapy/gene
on the Internet.)
- What are nonspecific immunomodulating agents?
Nonspecific immunomodulating agents are substances that stimulate or indirectly
augment the immune system. Often, these agents target key immune system cells
and cause secondary responses such as increased production of cytokines and
immunoglobulins. Two nonspecific immunomodulating agents used in cancer treatment
are bacillus
Calmette-Guerin (BCG)
and levamisole
.
BCG, which has been widely used as a tuberculosis vaccine, is used in the
treatment of superficial
bladder
cancer following surgery. BCG may work by stimulating an inflammatory,
and possibly an immune, response. A solution of BCG is instilled in the bladder
and stays there for about 2 hours before the patient is allowed to empty the
bladder by urinating. This treatment is usually performed once a week for
6 weeks.
Levamisole is sometimes used along with fluorouracil
(5FU) chemotherapy in the treatment of stage
III (DukesC) colon
cancer following surgery. Levamisole may act to restore depressed immune
function.
- Do biological therapies have any side effects?
Like other forms of cancer treatment, biological therapies can cause a number
of side effects, which can vary widely from agent to agent and patient to
patient. Rashes or swelling may develop at the site where the BRMs are injected.
Several BRMs, including interferons and interleukins, may cause flu-like symptoms
including fever, chills, nausea,
vomiting,
and appetite loss. Fatigue
is another common side effect of some BRMs. Blood pressure may also be affected.
The side effects of IL2 can often be severe, depending on the dosage
given. Patients need to be closely monitored during treatment with high doses
of IL2. Side effects of CSFs may include bone pain, fatigue, fever,
and appetite loss. The side effects of MOABs vary, and serious allergic reactions
may occur. Cancer vaccines can cause muscle aches and fever.
- Where can a person get more information about clinical trials?
Information about ongoing clinical trials involving these and other biological
therapies is available from the Cancer
Information Service (see below) or the clinical trials page of the NCI's
Web site at http://www.cancer.gov/clinicaltrials/
on the Internet.