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Medical research is giving new meaning to an old idea. Vaccines have been part of the infectious disease arsenal since they were first introduced to prevent smallpox more than 200 years ago. Traditionally, vaccines contain dead or weakened pathogens. Pathogens are disease-causing agents, such as viruses or bacteria. These agents stimulate the immune system to produce antibodies that fight future infections. In recent years, however, there have been new insights into how the immune system functions. These insights have encouraged scientists to explore novel approaches to vaccine therapy.
Today, new generations of vaccines are being developed to perform diverse tasks. One of the most active areas of vaccine research is the search for ways to “rev up” the immune system’s ability to fight cancer cells. Researchers are currently experimenting with vaccines to treat prostate cancer, melanoma (a form of skin cancer), and cancers of the colon, breast, pancreas, and kidneys.
The search for new prostate cancer therapies is especially vigorous because of the limitations of current treatments. The two most common treatments for early-stage prostate cancer are the surgical removal of the prostate gland and radiation therapy. Both cause serious side effects. One is impotence, the inability to maintain an erection. Another is incontinence, the inability to control the flow of urine. Hormone therapy lowers levels of male hormones, such as testosterone, that may stimulate the growth of prostate cancer cells. It is often used for more advanced prostate cancer. However, that treatment can produce side effects, such as breast enlargement and hot flashes. Chemotherapy is used for prostate cancer that is no longer responding to hormones. Its side effects can include nausea, vomiting, hair loss, and fatigue.
Faced with this daunting array of side effects, plus other limitations in treating prostate cancer, researchers are exploring new biological treatments that use the immune system to slow, stop, or reverse the disease. Biological treatments include substances that may boost the immune system. These include interferons, interleukins, monoclonal antibodies, as well as cancer vaccines.
To understand how cancer vaccines work, it helps to examine how the immune system works. It’s structured much like a military force. Scouts watch for invaders. Generals give orders on when to attack. Soldiers go into the field. And specialized weapons stop or kill invaders in different ways.
Scout cells of the immune system recognize invaders called antigens. When the scout cell spots an antigen, immune cells called B cells produce matching antibodies. The antibodies latch onto specific antigens in much the same way as a key fits into a lock. This activates other parts of the immune system, including T-cells and NK-cells, to attack the invaders.
T-cells are like the generals of the immune system. They direct and regulate the immune response by alerting other immune system defenders.
NK-cells (natural killer cells) are like soldiers. They destroy invaders by producing powerful chemicals that bind to and kill invading cells. Some white blood cells can be transformed into macrophages (literally big eaters), which physically consume invaders. They act like the special weapons of the immune system.
Prostate cancer vaccines are generally based on the antigens found on the surface of prostate cancer cells. Most vaccines are designed to stimulate T-cells. These T-cells orchestrate the response to invaders. Researchers are testing various strategies. One vaccine uses prostate-specific antigen (PSA), the blood marker measured in screening and monitoring tests for prostate cancer. Using genetic engineering techniques, the prostate-specific antigens are combined with a substance the body easily recognizes as foreign, such as a weakened virus. The goal of this type of vaccine is to re-educate the immune system to destroy not only the PSA-carrying virus, but also other PSA-carrying prostate cancer cells.
Another vaccine approach uses dendritic cells. These are a specialized form of white blood cells that are extracted from a patient’s blood. The dendritic cells are treated in the laboratory with proteins found on the surface of prostate cancer cells and then infused back into the patient. The goal is for the altered dendritic cells to attract the T-cells and trigger them to destroy other tumor cells that carry the same proteins.
A third vaccine approach ignores protein antigens on the surface of cancer cells and instead focuses on carbohydrate molecules that are unique to the surface of prostate cancer cells.
At least a half-dozen types of prostate cancer vaccines are being tested. Most are still considered experimental at this time, and are available only as part of clinical trials, which are studies designed to test the safety and effectiveness of new treatments. Patients interested in taking part in prostate cancer vaccine clinical trials should discuss eligibility with their oncologist. Studies generally limit enrollment to patients with specific medical histories and characteristics. While most clinical trials are conducted at major cancer centers, it's sometimes possible to participate under the care of your local doctor.
However, one prostate cancer vaccine, known as Provenge (sipuleucel-T), is now approved by the FDA. It is available to treat advanced prostate cancer that is no longer responding to hormones and is causing few or no symptoms.
Provenge is given as a series of three infusions, each about two weeks apart. A few days before each vaccine, the patient has some of his dendritic cells removed from his blood. The cells are sent to a lab, where they are exposed to a protein found on the surface of prostate cancer cells, along with a chemical to boost the immune response. The cells are then sent back to the doctor's office, where they are given back to the patient (similar to a blood transfusion).
In clinical trials, Provenge extended survival times of men with advanced prostate cancer by an average of about four months, although it does not cure prostate cancer. Side effects of Provenge tend to be mild, and can include fever, chills, fatigue, joint or back pain, headaches, and nausea.
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