Cancer Biological Therapies, Part 2

by National Cancer Institute

(Page 2 of 2)

Some examples of CSFs and their use in cancer therapy are as follows:

G-CSF (filgrastim) and GM-CSF (sargramostim) can increase the number of white blood cells, thereby reducing the risk of infection in patients receiving chemotherapy. G-CSF and GM-CSF 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's lymphoma. Herceptin is used to treat metastatic breast cancer in patients with tumors that produce excess amounts of a protein called HER-2. (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.

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 (5-FU) chemotherapy in the treatment of stage III (Dukes' C) 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 IL-2 can often be severe, depending on the dosage given. Patients need to be closely monitored during treatment with high doses of IL-2. 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.

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