EVERY YEAR, AMERICANS are advised to get a flu shot. The annual vaccine targets the strain of influenza that's anticipated to circulate that year and is given with the intent to prevent illness. The Centers for Disease Control and Prevention reports that "vaccines help develop immunity by imitating an infection, but this 'imitation' infection does not cause illness. Instead, it causes the immune system to develop the same response as it does to a real infection so the body can recognize and fight the vaccine-preventable disease in the future." Vaccines target antigens, such as viruses or bacteria, that enter the body and cause disease. The vaccine teaches the immune system that these antigens are dangerous and stimulates the immune system to develop antibodies – immune cells – that fight the antigen. This helps the body recognize disease-causing agents when they're next introduced to the body and fight them off. Broadly speaking, "a vaccine is really any treatment that's aimed at directing a patient's own immune system in a certain direction," says Dr. Seth M. Pollack, an oncologist and researcher at the Fred Hutchinson Cancer Research Center in Seattle. For decades, medical science has had effective vaccines against a variety of infectious diseases. More recently researchers have been developing vaccines for cancer. But it's a challenging proposition: Cancer is a fundamentally different disease from illnesses caused by infectious agents. Because cancer occurs when your own cells mutate and grow out of control, it isn't quite as easy to use the known vaccine technology to fight it. But researchers are looking for other ways to leverage the immune system to fight cancer in a manner that's similar to how a conventional vaccine works. Vaccines and Cancer Today Currently, you can get a vaccine against the human papillomavirus, which is a virus that can cause cervical cancer and cancers of the head and neck. The hepatitis B vaccine can also stave off the hepatitis B virus that has been associated with liver cancer. Both of those preventive vaccines are targeting a viral agent, not cancer cells, so they work in much the same way a flu vaccine does. In 2010, the Food and Drug Administration approved a vaccine called sipuleucel-T (Provenge) to treat prostate cancer. Unlike conventional vaccines, this treatment does not prevent the disease, but uses the patient's own dendritic cells (immune system cells) in combination with a protein to create an individualized treatment that targets the specific characteristics of that one person's cancer. "It was a pretty complex vaccine," says Dr. Esteban Celis, co-leader of the cancer immunology, inflammation and tolerance program at the Georgia Cancer Center at Augusta University in Augusta, Georgia. That vaccine requires "obtaining cells from the patient then modifying these cells and putting them back into the patient. The benefit of these vaccines was always a little bit questionable, and the price of doing this vaccine" can be prohibitive, he says. The added survival time only amounts to a few months in most patients, so Celis says this particular vaccine "is not a real winner" when you consider the cost versus the benefits. "Even for infectious disease, you have to take into account the risk-benefit ratio of any kind of vaccination. Like any kind of medical therapy, there's always risks of secondary negative effects," Celis says. The Future of Cancer Vaccines Looking toward the future of cancer vaccines, the focus is often on treating the disease after it has occurred rather than prevention. These treatments are classified as immunotherapiesbecause they are harnessing the patient's own immune system to fight cancer. Celis says his team is "using fragments of proteins that function as tumor-associated antigens called peptides," which can stimulate a strong immune response that helps the immune system kill the cancer itself. Some treatments are also being developed for use in combination with chemotherapy and other conventional treatments to augment the effects of those more traditional treatments. One problem with cancer vaccines currently in development is that the immune system response they trigger is often not strong enough to kill the cancer, and it doesn't last very long. "If you're going to try to treat people who have existent disease, the level of immune response has to be very high," Celis says. "Very few vaccines that have so far been tested in the clinic as vaccines are highly immunogenic – they don't induce strong enough immune responses." Therefore, they've only shown results against very small or early stage tumor masses and in preventing recurrence, and these effects fade quickly. "The immune system has memory. That's why you can receive a vaccine against a virus and be protected for many years," Celis says. But "in cancer, many of these vaccines fade away very fast, so you would have to continue to vaccinate periodically to sustain that response." And it's difficult to know when a patient's immune response has declined to the point of needing a booster. Although most vaccines for cancer are therapeutic vaccines, there is still hope that there could be a preventive cancer vaccine someday. But it's unlikely that such a vaccine will provide blanket protection against all cancers, Pollack says. "There almost certainly is not a universal target. The vaccine has to tell the immune system to go find something specific, but there's nothing specific that the immune system can look for that is common to all cancers," Pollack says. That's because cancer is not a single disease. Even within a certain body part, such as the breast, cancers vary greatly in how they grow, what causes them and which components can be exploited to kill them. Therefore, Celis says he thinks it's unlikely that we'll find a universal element of all cancers that can be used to create a blanket-coverage cancer vaccine. "Vaccines rely on an antigen, which is usually more specific for the kind of cancer. There's no indication that there's a universal antigen for cancer, although people are looking for them." Still, the search continues for a unifying element, even if it only applies to a few cancers. "There are some targets that are expressed by lots of cancers." Pollack says, including one called NY-ESO1 that's expressed in about 15 percent of cancers. Another protein that's being investigated is MUC1, which Celis says is expressed in several kinds of cancer, including breast, ovarian and lung. The work is promising, but he says, "I really doubt there's going to be one vaccine that's going to prevent all cancers." Therefore, targeting the population is important to moving forward with cancer vaccines. "If you're going to select a patient population to vaccinate before they ever get cancer, the most likely would be people genetically at high risk of developing cancer," Celis says. For example, women who have mutations on their BRCA1 or BRCA2 genes and have a significantly greater risk of developing breast cancer might one day have an option for a preventive vaccine. Currently, people with these mutations sometimes undergo preventive mastectomies or have their ovaries removed to drastically lower their risk of developing breast or ovarian cancer in the future. The hope is that someday, perhaps they could be vaccinated instead. "I would say that the chances of developing a prophylactic vaccine for those instances would be far greater than vaccinating the whole population against cancers," Celis says. But much more work needs to be done before such an option becomes available. Another patient population that may have options for vaccines in the not-too-distant future are those who have already had cancer. Celis and his team are working on therapies that could help reduce the chances of recurrence in certain patients. "Like with infectious disease, you wouldn't vaccinate everybody for Ebola, because we're not all at high risk of developing Ebola. You just have to identify who's at high risk of developing a disease and see what is the benefit of vaccinating." He says that there's always a risk of side effects with vaccines, so if the risk of developing the disease that vaccine is intended to prevent outweighs the chances you'll get it, there's no reason to vaccinate. "Why undergo that risk if you're not prone to develop that disease?" he asks. Pollack agrees that patients who've already had cancer are more likely candidates for vaccines than the general public "We'll first take people who are very high risk, for example people who've been diagnosed with and treated for cancer who have a high risk that the cancer would come back." In these patients, Pollack says the vaccine might be administered "right after chemotherapy in order to try and improve the time they get benefit from the chemotherapy." In this approach, the vaccine will augment the efficacy of the chemotherapy and may delay the cancer's recurrence. Immunotherapies and vaccines for cancer is a promising field of research that will likely change the way many different kinds of cancer are treated in the coming decades. Despite the challenges, Pollack says that he does think someday we'll be able to develop preventive vaccines that will stop some cancers before they start, but "it's a long way off." Source
