When we think of vaccines, we think of a shot given to a healthy subject to prevent them from becoming infected with the disease the vaccine targets. This type of preventive vaccine has worked well for many diseases, and there are now more than 20 vaccines commonly used in the United States for diseases including polio, rabies, tetanus, measles, and now, COVID-19.
Developing a preventive vaccine for cancer is more difficult. Unlike the usual vaccine targets—foreign viruses or bacteria—cancer cells look very similar to our normal, healthy cells, so the immune system sometimes doesn’t recognize them as invaders and doesn’t mobilize to attack them. Also, cancer is not homogenous—there are many different types of cancer and each tumor is different, so a vaccine for one type of cancer likely would not work for a different type.
There are only four approved vaccines that will prevent cancer from occurring in healthy people, and all of them protect against a virus: there are three different vaccines for HPV (human papilloma virus), which causes several types of cancer, including cervical and anal cancer; and one vaccine for hepatitis B, which can cause liver cancer.
Another type of vaccine, called a treatment or therapeutic vaccine because it treats existing cancer, uses a different approach: immunotherapy. Rather than preventing cancer in healthy subjects, these immunotherapy vaccines motivate the immune system to attack cancer cells in order to stop tumors from spreading or growing, destroy any cancers cells remaining in the body after the primary cancer treatment, or stop successfully treated cancer from coming back.
There are two approved immunotherapy vaccines: Bacillus Calmette-Guérin, a previously approved preventive vaccine for tuberculosis that is now approved for patients with early-stage bladder cancer, and Sipuleucel-T, approved since 2010 to treat prostate cancer.
While only two therapeutic cancer vaccines have reached the approval stage, and they only work for specific types of cancer, several more experimental cancer vaccines are in the works.
A Cancer Vaccine That Combines Immunotherapy with Chemotherapy
Chemotherapy and immunotherapy each offer strong, if not perfect methods of treating cancer. Chemotherapy is very effective at killing cancer cells, but it also damages healthy cells and does not always prevent cancer from spreading or recurring. Immunotherapy, which prompts the immune system to target cancer cells, generates a longer-term anti-cancer response in the body, but can’t always target specific tumors or difficult to treat cancer types.
Now, a cancer vaccine candidate 10 years in the making combines the power of chemotherapy and immunotherapy into a single “cancer vaccine” than can be injected near the tumor site. The chemotherapy portion of the vaccine kills cancer cells and reduces tumor growth, and the immunotherapy portion of the vaccine mobilizes immune cells to attack the tumor.
The vaccine was tested on mice with triple-negative breast cancer, one of the most aggressive and difficult to treat types of cancer. When injected with the vaccine, 100% of the triple-negative mice survived an injection of additional cancer cells without relapsing. The mice with triple-negative breast cancer that did not receive the vaccine all died of the disease after being injected with new cancer cells.
In further tests, the researchers added a checkpoint inhibitor designed to block the tumor’s ability to evade the immune system to the vaccine cocktail and discovered that it further reduced the growth of tumors and increased the life span of the mice.
The research team is working on optimizing the vaccine for other types of cancer, and has hopes to move into preclinical and human trials.
Another experimental vaccine for triple-negative breast cancer, which targets alpha-lactalbumin, a protein in women’s mammary glands that is often present in triple negative breast cancer cases, has proven effective at preventing triple negative breast cancer in mice. The vaccine, developed by the Cleveland Clinic, has received FDA clearance to move to human clinical trials, which are expected to begin in spring of 2021.
A Personalized Vaccine, with an Extra Boost
In addition to its FDA-approved mRNA COVID-19 vaccine, Moderna has also developed an mRNA-based personalized cancer vaccine called mRNA-4157. Unlike immunotherapy vaccines, personalized vaccines are based on the individual’s specific cancer type, and sometimes the patient’s own cells.
mRNA-4157 works by predicting the molecules, based on a patient’s cancer type, that will stimulate the immune system to attack that particular cancer. The mRNA can encode up to 34 of these neoantigens into a single vaccine. Once injected, the vaccine releases the neoantigens, stimulating the immune system to attack the cancer cells.
The vaccine is being tested in combination with a checkpoint inhibitor developed by Merck called Keytruda (pembrolizumab), which inhibits the tumor’s ability to block T-cell responses.
Keytruda has also been shown to increase the efficacy of other experimental cancer vaccines, including those for melanoma and ovarian cancer.
A phase 1 clinical trial showed that Keytruda combined with UV1, an experimental cancer vaccine developed by Ultimovacs, is effective in treating metastatic melanoma.
Keytruda also boosted the effectiveness of DSP-7888, an investigational cancer vaccine for advanced malignancies developed by Boston Biomedical, in a phase 2 trial testing the effectiveness of the vaccine against platinum-resistant ovarian cancer.
When it comes to cancer vaccines, despite decades of work, the science still has a long way to go. But recent progress toward finding a more effective way to treat and prevent cancer using vaccines is sign that cancer vaccines may someday become as commonplace as flu shots.
