We’re told to get a flu shot every year, and most Americans are vaccinated against various diseases including mumps, measles and whooping cough as children. But what are the chances you someday might be able to get a vaccine to prevent breast cancer?
The National Institutes of Health report that “vaccines take advantage of your body’s natural ability to learn how to combat many disease-causing germs, or microbes, that attack it. What’s more, your body ‘remembers’ how to protect itself from the microbes it has encountered before.” Most common vaccines target viruses by “teaching” the immune system to create antibodies — protein molecules that fight the invading virus, which is called an antigen — when the virus is present in the body. Cancer is fundamentally different from viruses in that it’s your own cells made from your own genetic material that have gone a bit haywire in the way they proliferate, but researchers are hard at work developing agents that can stimulate a similar immune response by teaching the immune system to recognize certain proteins on the surface of cancer cells as antigens.
Dr. Pravin T.P. Kaumaya, professor of medicine in the department of Ob/Gyn at the Wexner Medical Center and director of the division of vaccine development/peptide and protein engineering laboratory at The Ohio State University, has been working on developing a vaccine for breast cancer for much of his career and currently has an ongoing clinical trial studying the efficacy of a vaccine that targets HER2-positive breast cancer. “We’re dealing with this particular case with breast cancer and cancers that overexpress this HER2 oncogene,” Kaumaya says. An oncogene is a gene that has the potential to transform a cell into a tumor cell when it mutates. These mutations can be caused by genetics or environmental factors. Human epidermal growth factor receptor 2, or HER2 for short, is a protein involved in the normal growth of cells. But in some types of cancer, a mutation in the cells leads to an overproduction, or overexpression, of this HER2 protein on their surface, which can cause tumor cells to grow and proliferate.
The Dana-Farber Cancer Institute reports that about 20 percent of breast cancers overexpress HER2. “It is thought that signaling through the HER2 receptor is vital for the normal growth and spread of breast cells. Cancers that are HER2-positive can have either too many copies of the HER2 gene, or too many copies of the HER2 receptor, which causes cancer cells to grow,” the DFCI reports.
[See: 7 Innovations in Cancer Therapy.]
HER2 is also sometimes overexpressed in lung, ovarian, bladder, colon and gastric/esophageal cancers. “Not all cancers express the HER2 oncogene, and I don’t think we’ve isolated or identified a universal agent or oncogene that can be used in a number of different cancers,” Kaumaya says. But many researchers are actively investigating other oncogenes and looking for ways to exploit their overexpression to shut down other types of cancer. The idea is that if you can find the genetic driver of the cancer and mark it as an antigen, your immune system can take up the fight from there on its own.
The challenge, Kaumaya says, lies in getting the immune system to respond to only the cancer cells instead of other tissues in the body. “It’s easier to generate a vaccine to a viral antigen, like with the flu,” because it has different genetic material that’s come from outside the body. With cancer, the cells are your own genetic material, so researchers are looking for other ways into the cell to shut it down. Oncogenes like HER2 have become prime targets for this type of treatment because their overexpression gives the vaccine a target. “The only reason we’ve been successful is because of the overexpression of the antigens in those various cancers,” Kaumaya says.
Dr. Brian Czerniecki, chair and senior member in the Moffitt Cancer Center Department of Breast Oncology in Tampa, has also been working on developing a vaccine for HER2-positive breast cancer and is currently conducting a clinical trial to determine the efficacy of a vaccine that’s made from a patient’s own white blood cells.
This personalized form of treatment uses the patient’s “own immune response and replaces and restores something that’s now missing,” he says. That missing something is CD4 cells. Also called T cells, T lymphocytes or helper T cells, CD4 cells are white blood cells that indicate the health of your immune system. When their number drops, that means the immune system is fighting off something. (CD4 cells are also implicated in HIV and AIDS.)
[See: A Tour of Mammographic Screenings During Your Life.]
Cancer cells have a knack for eluding the immune system, and one way they do that is by exploiting immune checkpoints, proteins on the cells that prevent the immune system from attacking the cell. Ongoing research into immunotherapy for cancer has resulted in a class of drugs called checkpoint inhibitors, which are made from antibodies and can prevent the cancer from “hiding” behind the checkpoint. This action exposes cancer cells more readily to the effects of the immune system. These drugs are showing promise, but they don’t always work well, and Czerniecki says that could be because there aren’t enough CD4 cells left in the body to mount an adequate attack on the cancer cells once the immune system can see them as antigens. “We’ve found in mice that we give breast cancer to, unless you restock the CD4, those checkpoint inhibitors don’t work. But if you get that CD4 response driven back up, then the checkpoints start to work,” and the body can begin to fight the cancer with its own defenses.
To simplify the discussion of how this process works, Czerniecki offers an analogy that may be more familiar to most people. “I can relate it to vitamin C and scurvy,” he says. (Scurvy is a rare condition in which a severe lack of vitamin C in the diet can lead to anemia, bleeding gums, rashes and even death if left untreated.) “If you have vitamin C, you don’t get scurvy, but if you’re deficient in vitamin C you get scurvy.” If you replace the vitamin C that’s missing, “your disease goes away,” and he says the vaccine “may be similar to this, especially if we can catch things early.”
He notes that vaccines won’t work “as a stand-alone [treatment] in stage 4 metastatic breast cancer. The place where it’s going to have an impact is in early stage disease, in these people who have residual disease after neoadjuvant chemotherapy,” meaning they had chemotherapy before another treatment such as surgery or radiation, “but they have tumor cells that are hiding out somewhere. That’s when the immune system is probably going to work its best. Or in early stages, such as DCIS,” ductal carcinoma in situ, which means abnormal cells are present in a milk duct. DCIS is considered the earliest stage of breast cancer. “Other places where vaccines will work best is as adjuncts,” or alongside other forms of treatment. “They’ll make chemo work better, they can make radiation work better. So it’s going to be a component of the therapy, but they probably won’t always stand alone,” he says.
Vaccines may also be useful in preventing recurrence of breast cancer, Czerniecki says. Once the body’s immune response has been triggered, the immune system will “see” cancer cells as antigens, or foreign invaders, and “remember” them in the future, meaning these vaccines could potentially teach your body to fight off breast cancer if it recurs later. Science is still in the early days of these technologies, but hope runs high that there will be a safe and effective vaccine for a number of different cancers in the not-too-distant future.
[See: What Not to Say to a Breast Cancer Patient.]
Although the vaccines currently in development for breast and a few other types of cancer are intended as treatments after a cancer has begun to grow, the greater hope is that in the future, preventive vaccines could be developed to ward off a cancer before it even gains a foothold. “At the moment, most of the procedures are therapeutic, and what we want is a preventive vaccine,” Kaumaya says. Czerniecki agrees, saying that if we can design a vaccine that effectively targets oncogenes in people with certain high-risk genetic mutations, “you could come up with a scenario where we could maybe vaccinate people who are at higher risk to prevent the cancer” from ever starting.” He says one day we might have a blood test that looks at the health of your immune system to “predict that you’re at risk of getting something and we can fix it before you get it.”
Such a possibility would give a whole new meaning to the idea of keeping up-to-date with your inoculations.
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Will There Be a Vaccine for Breast Cancer Someday? originally appeared on usnews.com
