msn.com May 31, 2009
ORLANDO, Fla. - First there was surgery, then chemotherapy and radiation. Now, doctors have overcome 30 years of false starts and found success with a fourth way to fight cancer: using the body’s natural defender, the immune system.
The approach is called a cancer vaccine, although it treats the disease rather than prevents it.
At a cancer conference Sunday, researchers said one such vaccine kept a common form of lymphoma from worsening for more than a year. That’s huge in this field, where progress is glacial and success with a new treatment is often measured in weeks or even days.
“I don’t know what we did differently to make the breakthrough,” said Dr. Len Lichtenfeld of the American Cancer Society.
Instead of a single “A-Ha!” moment, there have been many “ah, so” discoveries about the immune system that now seem to be paying off, said Dr. John Niederhuber, director of the National Cancer Institute.
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It’s way too soon to declare victory. No one knows how long the benefits will last, whether people will need “boosters” to keep their disease in check, or whether vaccines will ever be a cure. Many vaccines must be custom-made for each patient. How practical will that be, and what will it cost?
Those are all good questions — but there are no answers yet, said Dr. Richard Schilsky, a University of Chicago cancer specialist who is president of the American Society of Clinical Oncology.
Several vaccine studies were reported over the weekend at the oncology group’s annual meeting in Florida.
A big problem has been getting the immune system to “see” cancer as a threat, said Dr. Patrick Hwu, melanoma chief at the University of Texas M.D. Anderson Cancer Center. Viruses like the flu or polio are easily spotted by the immune system because they look different from human cells.
“But cancer comes from our own cells. And so it’s more like guerrilla warfare — the immune system has trouble distinguishing the normal cells from the cancer cells,” he said.
To help it do that, many cancer vaccines take a substance from a cancer cell’s surface and attach it to something the immune system already recognizes as foreign — in the lymphoma vaccine’s case, a shellfish protein.
“It’s a mimic to what you’re trying to kill, a training device to train the immune system to kill something,” Hwu explained.
Putting immune system on high alert
To make the attack as strong as possible, doctors add a substance to put the immune system on high alert.
Dr. Stephen Schuster of the University of Pennsylvania School of Medicine led a study testing BiovaxID, an experimental vaccine against follicular lymphoma developed by the National Cancer Institute. Rights to it are now held by Biovest International Inc. of Worcester, Mass., and some of his co-researchers have financial ties to the company.
To be in the study, patients had to have achieved a remission for at least six months with standard chemo. This often occurs with this type of lymphoma, but the disease usually comes back.
Researchers gave 41 patients the shellfish protein and an immune booster; 76 other patients were given those plus the vaccine. After nearly five years of followup, the average time until the cancer worsened was 44 months in the vaccine group and 30 months in the others.
Big gains also were seen with a neuroblastoma vaccine developed by the cancer institute. In a study of 226 patients, 86 percent of vaccine recipients were still alive after two years versus 75 percent of others not given the vaccine. Results were released by the oncology society two weeks ago.
The benefits from a melanoma vaccine developed by the cancer institute were more modest. It extended the time until patients relapsed — three months versus one and a half for those not given the vaccine.
Hilde Stapleton, 53, of suburban Houston, is one of the lucky ones it helped. Still, she found what many other vaccine recipients have learned: The vaccine had few side effects, but the immune system boosters were “like the worst case of flu you’ve ever had,” she said.
The prostate cancer vaccine, Provenge, is farthest along. Its maker, Seattle-based Dendreon Corp., is seeking federal Food and Drug Administration approval for it. A study last month found that it extended survival by four months in men with very advanced disease.
Doctors unconnected with these experiments are cautiously optimistic.
“We’ve raised so many false hopes in the past,” said Lichtenfeld of the Cancer Society. “What’s different this time is we have the science reports to back up improvements.”
FROM THE NATIONAL CANCER INSTITUTE:
What are vaccines?
The immune system is a complex network of organs, tissues, and specialized cells that act collectively to defend the body. When a particular type of microbe invades the body, the immune system recognizes it as foreign, destroys it, and “remembers” it to prevent another infection. Vaccines take advantage of this response. Traditional vaccines usually contain harmless versions of microbes—killed or weakened microbes, or parts of microbes—that do not cause disease but are able to stimulate an immune response. When the immune system encounters these substances through vaccination, it responds to them, eliminates them from the body, and develops a memory of them. This vaccine-induced memory enables the immune system to act quickly to protect the body if it becomes infected by the same microbe in the future.
The immune system’s role in defending against disease-causing microbes has long been recognized. Scientists have also discovered that the immune system can protect the body against threats posed by certain types of damaged, diseased, or abnormal cells, including cancer cells.
How do vaccines stimulate the immune system?
White blood cells, or leukocytes, play the main role in immune responses. These cells carry out the many tasks required to protect the body against disease-causing microbes and abnormal cells. Some types of leukocytes patrol the body, seeking foreign invaders and diseased, damaged, or dead cells. These white blood cells provide a general—or nonspecific—level of immune protection. Other types of leukocytes, known as lymphocytes, provide targeted protection against specific threats, whether from a specific microbe or a diseased or abnormal cell. The most important groups of lymphocytes responsible for carrying out immune responses against such threats are B cells and cytotoxic (cell-killing) T cells. B cells make antibodies, which are large proteins secreted by B cells that bind to, inactivate, and help destroy foreign invaders or abnormal cells. Most preventive vaccines, including those aimed at hepatitis B virus (HBV) and human papillomavirus (HPV), stimulate the production of antibodies that bind to specific, targeted microbes and block their ability to cause infection. Cytotoxic T cells, which are also known as killer T cells, kill infected or abnormal cells by releasing toxic chemicals or by prompting the cells to self-destruct (apoptosis).
Other types of lymphocytes and leukocytes play supporting roles to ensure that B cells and killer T cells do their jobs effectively. Cells that help fine-tune the activities of B cells and killer T cells include helper T cells and dendritic cells, which help activate killer T cells and enable them to recognize specific threats. Cancer treatment vaccines work by activating B cells and killer T cells and directing them to recognize and act against specific types of cancer. They do this by introducing one or more molecules known as antigens into the body, usually by injection. An antigen is a substance that stimulates a specific immune response. An antigen can be a protein or another type of molecule found on the surface of or inside a cell.
Microbes carry antigens that “tell” the immune system they are foreign—or “non-self”—and, therefore, represent a potential threat that should be destroyed. In contrast, normal cells in the body have antigens that identify them as “self.” Self antigens tell the immune system that normal cells are not a threat and should be ignored. Cancer cells can carry both types of antigens. They have self antigens, which they share in common with normal cells, but they may also have antigens that are unique to cancer cells. These cancer-associated antigens mark cancer cells as abnormal, or non-self, and can cause B cells and killer T cells to mount an attack against the cancer.
Cancer cells may also make much larger than normal amounts of certain self antigens. These overly abundant self antigens may be viewed by the immune system as being foreign and, therefore, may trigger an immune response against the cancer.
What are cancer vaccines?
Cancer vaccines are medicines that belong to a class of substances known as biological response modifiers. Biological response modifiers work by stimulating or restoring the immune system’s ability to fight infections and disease. There are two broad types of cancer vaccines:
Preventive (or prophylactic) vaccines, which are intended to prevent cancer from developing in healthy people; and Treatment (or therapeutic) vaccines, which are intended to treat already existing cancers by strengthening the body's natural defenses against cancer.
Two types of cancer preventive vaccines have been successfully developed and are available in the United States. However, cancer treatment vaccines remain an experimental form of therapy.
How do cancer preventive vaccines work?
Cancer preventive vaccines target infectious agents that cause or contribute to the development of cancer. They are similar to traditional vaccines, which help prevent infectious diseases such as measles or polio by protecting the body against infection. Both cancer preventive vaccines and traditional vaccines are based on antigens that are carried by the infectious agents and that are relatively easy for the immune system to recognize as foreign.
Have any cancer preventive vaccines been approved for use in the United States?
In 2006, the U.S. Food and Drug Administration (FDA) approved the vaccine known as Gardasil®, which protects against infection by two types of HPV—specifically, types 16 and 18—that cause approximately 70 percent of all cases of cervical cancer worldwide. At least 17 other types of HPV are responsible for the remaining 30 percent of cervical cancer cases (9). Gardasil also protects against HPV types 6 and 11, which are responsible for about 90 percent of all cases of genital warts. However, these two HPV types do not cause cervical cancer.
In 2008, the FDA expanded Gardasil’s approval to include its use in the prevention of HPV-associated vulvar and vaginal cancers. Gardasil, manufactured by Merck & Company, is based on HPV antigens that are proteins. These proteins are used in the laboratory to make four different types of “virus-like particles,” or VLPs, which correspond to HPV types 6, 11, 16, and 18. The four types of VLPs are then combined to make the vaccine. Because Gardasil targets four HPV types, it is called a quadrivalent vaccine (10). In contrast with traditional vaccines, which are often composed of weakened, whole microbes, the VLPs in Gardasil are not infectious. However, they are still able to stimulate the production of antibodies against HPV types 6, 11, 16, and 18.
A second HPV vaccine manufactured by GlaxoSmithKline and known by the name Cervarix® has also been developed. Although Cervarix has been approved for use in Europe, it has not yet been approved by the FDA for use in the United States. In contrast with Gardasil, Cervarix is a bivalent vaccine. It is composed of VLPs made with proteins from HPV types 16 and 18. Therefore, it provides protection only against these two HPV types. The public health benefits of vaccines against HPV types 16 and 18 may extend beyond reducing the risks of cervical cancer, vaginal cancer, and vulvar cancer. Evidence suggests that chronic infection by one or both of these virus types is also associated with cancers of the anus, penis, and oropharynx.
The FDA has approved one other type of cancer preventive vaccine, which protects against HBV infection. Chronic HBV infection can lead to liver cancer. The first HBV vaccine was approved in 1981, making it the first cancer preventive vaccine to be successfully developed and marketed. Today, most children in the United States are vaccinated against HBV shortly after birth.
