A small new clinical trial has investigated a personalized cancer vaccine for people with head and neck cancer. Lesterman/Shutterstock.com
Promising results have come out of a new clinical trial investigating a personalized cancer vaccine for people with head and neck cancer. The researchers note that it's a very small study and still preliminary work, but their early results are looking good.
In a phase 1 trial, scientists at the University of Arizona Health Sciences set out to study the safety and effectiveness of a personalized cancer vaccine, combined with the immunotherapy drug Pembrolizumab, for the treatment of 10 people with head and neck cancer. Their findings showed that half of the patients positively responded to the treatment, while two patients received a complete response after the treatment, meaning there was no detectable cancer present.
“The data are preliminary and the sample size is small, but it is promising,” Dr Julie E Bauman, deputy director of the University of Arizona Cancer Center and a professor of medicine and chief of the Division of Hematology and Oncology at the UArizona College of Medicine – Tucson, said in a statement.
“A phase I trial is about safety first and foremost, and we now know this treatment is safe and tolerable. But, we also have a strong signal to point us to further study this in head and neck cancer. That is why we are excited to expand this trial."
Personalized cancer vaccines are one of the extremely promising new ways researchers are looking to fight cancer. Although much more complex, it essentially works on the same principle as any vaccine: it provides the immune system with a sample of what it should fight. Most vaccines, such as for measles or polio, are preventive, but cancer vaccines do not prevent the disease. Instead, they are typically given to people already diagnosed with cancer as a treatment that aims to boost the body's natural defense.
Cancers vary wildly from person to person. Cancer cells are the product of genetic mutations and these mutations are different for each patient. To pinpoint patient-specific cancer, the mutated DNA of the patient's cancerous tumor is simultaneously sequenced alongside healthy DNA from their blood. This identifies the patient’s unique mutations, which are then coded into a single molecule of messenger RNA (mRNA) and made into a vaccine. Once the vaccine is administered, it helps the body’s immune cells to learn to identify and attack the mutated cancer cells.
Much of the research into this approach is still in its very early days and biomedicine progress can be notoriously long and arduous. Nevertheless, many are extremely excited about the potential held by personalized medicine and the prospect of personalized cancer vaccines.
Off the back of this success, the team will now expand the trials to 40 more patients with head and neck cancer, a relatively uncommon type of cancer that generally refers to cancers in the larynx, throat, lips, mouth, nose, and salivary glands.
Since the first vaccine for smallpox was developed by English physician Edward Jenner in 1796, vaccines have prevented a variety of devastating maladies and saved millions of lives. The World Health Organization lists 26 available vaccines—for diseases from cholera to yellow fever—and another two dozen are in development for illnesses like malaria and the Zika virus. Not on the list of diseases targeted by current or potential vaccines: cancer. In fact, despite advances in medicine, and in cancer treatment in particular, one unfortunate scientific reality is that a universal vaccine to prevent cancer will likely never be developed. "Biologically impossible," says Maurie Markman, MD, President of Medicine & Science at Cancer Treatment Centers of America® (CTCA). "There can't be a vaccine for cancer because cancer isn't a single entity. It's thousands of different conditions."
Vaccines play a vital role in the prevention of some cancers and in the treatment of others, and they are an essential tool in protecting cancer patients during treatments that may make them more vulnerable to illnesses.
Still, vaccines play a vital role in the prevention of some cancers and in the treatment of others, and they are an essential tool in protecting cancer patients during treatments that may make them more vulnerable to illnesses. Scientists are also researching new personalized cancer vaccines that have shown positive results in clinical trials as a potential treatment for some patients with melanoma, among the most challenging cancers.
Vaccines geared specifically to cancer come in two categories: those designed to prevent some forms of the disease, and those designed to treat it.
- Prophylactic or preventative vaccines: Only two such vaccines are currently in use, and neither directly prevents cancer. Instead, the vaccines work by killing viruses that may lead to cancer. The human papillomavirus (HPV) vaccine, for example, targets potent strains of HPV that cause the majority of cervical, throat, anal and several other cancers. The hepatitis B vaccine is designed to help prevent some cases of liver cancer. "These vaccines prevent viruses that cause inflammation that may lead to cancer," says Stephen Lynch, MD, Primary Care and Intake Physician at our hospital near Phoenix. Other viruses, such as HIV, also may lead to cancer, but so far, no vaccines have been developed to prevent them.
- Therapeutic or treatment vaccines: These are designed to stimulate the immune system to attack cancer cells. Two therapeutic cancer vaccines are now in use: Sipuleucel-T (Provenge®), which may help treat advanced prostate cancer, and the Bacillus Calmette–Guérin (BCG) vaccine, which was originally developed for tuberculosis and has since been approved to treat bladder cancer. "These can be very useful," Dr. Markman says. "They are very potent immune stimulants."
While some vaccines are being used to help prevent and treat certain cancers, some scientists doubt whether those uses can be expanded in a meaningful way, especially since research into new cancer vaccines has not yielded the results many hoped. "The history of cancer vaccines is a history of failure," writes one author who chronicled the decades-old frustration over cancer vaccine research. Other researchers, though, are not giving up, and a variety of clinical trials are exploring potential new vaccines for a variety of cancers.
Still, they continue to be stumped by a persistent question: What should the cancer vaccine target? Scores of cancers are caused by a multitude of gene mutations, so developing a vaccine to target all possible mutations is likely impossible. And since cancer cells are the body's own cells gone rogue, many cancer cells are able to hide in plain sight from the immune system. That’s why, even when the immune system is stimulated by certain drugs, it doesn't always know what targets to attack. "First of all, you have to identify something that's targetable for your immune system," Dr. Lynch says. "The intent of the vaccine is to generate an immune response, to have soldiers on watch to attack when presented by an antigen, bacteria or a virus. So you have to identify a pathogen that you can target with a vaccine. That's the great mystery."
Buoyed by advances in immunotherapy, cancer vaccine research is back in the spotlight. Several research projects are exploring personalized cancer vaccines, similar to sipuleucel-T, that use specialized dendritic cells to trigger an immune response. Dendritic cells are messenger cells that alert T-cells to the presence of antigens, which are proteins found on many cancer cells, differentiating them from normal cells. Researchers take pieces of proteins from cancer cells, called peptides, from a patient, attach them to dendritic cells and inject them back into the patient. When the vaccine works as designed, the dendritic cells reveal the peptides to T-cells, which seek out those proteins and attack them.
Researchers in Boston are exploring a similar approach, using neoantigens specific to cancer cells to create a vaccine for patients with advanced melanoma. Neoantigens are new antigens that may develop on cancer cells. Researchers identify several neoantigens and use computer algorithms to determine potential targets that may be used to develop a treatment vaccine. "Neoantigens are a very attractive target as a vaccine because they are novel antigens similar to a virus that are potentially much more visible to the immune system than antigens previously used in cancer vaccines. The mutated antigen is present only in the tumor, not in normal cells," researcher Patrick A. Ott, MD, PhD, told Ascopost.com.
Separate from vaccines designed to treat and prevent cancer are those that are being used as a critical tool in helping cancer patients stay healthy during and after treatment. Some cancer treatments, such as chemotherapy and stem cell or bone marrow transplants, may severely compromise the patient's immune system. That’s why it’s so important that cancer patients, and their caregivers and family members, receive vaccines for the flu and other preventable illnesses. "Cancer patients who have suppressed immune systems need certain vaccines to prevent infection," says Mashiul Chowdhury, MD, Chief of the Division of Infectious Disease for CTCA® and Internist at our hospital in Philadelphia. "We encourage cancer patients to receive certain adult immunizations, because if they have pneumonia or a viral disease, it’s usually much more severe in cancer patients, and the outcome can be very more serious."
“ We encourage cancer patients to receive certain adult immunizations, because if they have pneumonia or a viral disease, it’s usually much more severe in cancer patients, and the outcome can be very more serious.”
-Mashiul Chowdhury, MD, Chief of the Division of Infectious Disease for CTCA®
Dr. Chowdhury recommends doctors and patients follow the immunization protocol for adults established by the Centers for Disease Control and Prevention (CDC). That includes an annual flu vaccine. Cancer patients may also need to avoid live vaccines, or those that use live viruses to inoculate against disease. "If you give live virus vaccines to an immune-suppressed patient, the virus can duplicate and the patient can get those infections instead of preventing infections," Dr. Chowdhury says. Patients should also avoid contact with people who have received live vaccines for the same reason. Also, patients who have had stem cell or bone marrow transplants may need boosters or new vaccinations at some point after treatment, because such transplants often reverse the immunization effect of previous vaccines.
One of the biggest challenges in keeping patients healthy during treatment, though, is convincing them to actually get vaccinated. "A significant number of people are afraid of vaccines," Dr. Chowdhury says. Conspiracy theories linking vaccines to autism or other conditions have prompted some parents to refuse vaccinations for their children. But the risks of avoiding vaccinations are high. In 2017, a measles outbreak in Minnesota sickened 79 people, many of them unvaccinated children. And more than 125 people infected in California were linked to trips to Disneyland. A survey by the CDC showed that 28 of those patients were intentionally unvaccinated because of personal beliefs. "There is absolutely no scientific evidence of vaccines causing autism," Dr. Chowdhury says. "It's very frustrating."
Despite overwhelming evidence that the HPV virus may prevent cancer, the numbers of girls and young adult women getting the HPV vaccine are still very low. And the number of boys and young men who are vaccinated is even lower—less than 11 percent of male candidates for the HPV vaccine have received it. As a consequence, the rate of HPV-related head and neck cancers in men has surpassed that of cervical cancer in women. "It's a serious problem," Dr. Markman says, "when we have vaccines that have been shown to reduce cancer rates, and people will not use them."
