December 17, 2022
Messenger RNA technology, a key component of the most commonly used COVID-19 vaccines in the United States, was first developed as a tool to combat cancer. Now, the success of those coronavirus shots has left many scientists optimistic that mRNA can indeed be used to reduce cancer deaths.
Early evidence arrived last week when Moderna released data on its experimental mRNA-based vaccine for melanoma, the most serious type of skin cancer. In a small study, melanoma patients who were given the vaccine with Keytruda, a cancer immunotherapy drug manufactured by Merck, were 44% less likely to have a recurrence or die compared to those who only received Keytruda.
Serious adverse events were reported in 14.4% of the patients who received the vaccine and the drug, and in 10% of those who had received just Keytruda.
"Today's results are highly encouraging for the field of cancer treatment," Stéphane Bancel, Moderna's chief executive, said Wednesday. "mRNA has been transformative for COVID-19, and now, for the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomized clinical trial in melanoma."
Moderna and Merck have not released the full results of the study, which involved 157 patients with melanomas that had spread to their lymph nodes, creating a high risk of recurrence. The next step in testing the vaccine will be a larger study, which could begin next year.
But the vaccine is far from the only mRNA-based cancer vaccine being developed. There have been small trials of similar vaccines for nearly a decade, with some encouraging results. The success of the COVID-19 vaccines has helped accelerate that research, scientists say.
"There's a lot of enthusiasm around mRNA right now," Dr. Patrick Ott, who directs the Center for Personal Cancer Vaccines at the Dana-Farber Cancer Institute in Boston said earlier this year. "The funding and resources that are flowing into mRNA vaccine research will help the cancer vaccine field."
BioNTech, the German biotechnology company that helped Pfizer develop a COVID-19 shot, was founded in 2008 with the intention of exploring the potential of mRNA to treat cancer. Though the company's mission pivoted when the COVID-19 pandemic began, it still has mRNA-based cancer vaccines in various stages of testing. They include vaccines for advanced melanoma, head and neck cancers, prostate cancer and non-small cell lung cancer.
Other pharmaceutical companies and research institutions have jumped into this area of research as well.
In May, CureVac, a German biopharmaceutical company, said it was "translating the important insights and findings" gained from its research on mRNA-based COVID-19 and influenza vaccines to its oncology program. And the Dana-Farber Cancer Institute has mRNA to develop a personalized melanoma vaccine that it is testing.
"Multiple cancer and infectious disease mRNA vaccine clinical trials are underway and the next couple of years will be really exciting and tell us more about the range of applicability of mRNA vaccines," Norbert Pardi, a research assistant professor of infectious diseases at the University of Pennsylvania noted last year.
Traditionally, vaccines have been designed to prevent infectious diseases caused by bacteria or viruses. Preventive cancer vaccines are more challenging to develop because cancers have more complex causes. Cancer cells tend to look very similar to healthy cells, and each tumor tends to exhibit unique mutations. But for some types of cancers, therapeutic vaccines can effectively reduce the recurrence of tumors after a person has been diagnosed.
Currently, there are four preventive cancer vaccines that have been approved by the U.S. Food and Drug Administration. Three of them protect against human papillomavirus, or HPV, which can cause anal, cervical, head and neck, penile, vulvar and vagina cancers. The other is a hepatitis B vaccine, which protects against hepatitis B-related liver cancer, as well as infections caused by the virus.
There also are two therapeutic cancer vaccines. One uses weakened bacteria to treat early-stage bladder cancer; the other uses a patient's own immune cells to treat prostate cancer.
The FDA has not approved any mRNA-based cancer vaccines. Should a therapeutic vaccine reach that point, scientists will then need to determine who to best combine the vaccine with the gold standards of cancer treatment: surgery, radiation and chemotherapy.
Vaccines that utilize mRNA technology instruct cells to produce an antigen – a protein – that help the immune system identify threats. The targeted protein in COVID-19 vaccines is part of the spike on the coronavirus. Cancer vaccines target a marker on the surface of tumor cells.
Messenger RNA technology, which was advanced by scientists at Penn, is being used to target cancer in two ways: by going after antigens that are shared by cancer patients and going after patient-specific antigens.
The more personalized vaccines use samples from patients' cancer cells and healthy tissues to identify the mutations of their specific tumors. This allows the vaccine to be tailored specifically to fight their cancers.
But this is a major challenge because these vaccines have to be highly personal to be effective, scientists say. The majority of everyone's tumors neoantigens – new proteins that grow on cancerous cells following mutations – are specific to them.
"That's why we need a vaccine technology that is flexible and potent, such as the mRNA technology used for COVID-19," Pardi said last year. "It could be developed to give us personalized neoantigen vaccines."
