mRNA Vaccines in the Fight Against Cancer

By Mike Howie

The COVID-19 pandemic and resulting vaccines from BioNTech–Pfizer and Moderna brought broad public attention to mRNA vaccines. While some were excited by the speed with which the vaccines were developed and their reported efficacy, others were skeptical of the technology. mRNA vaccines in general had never been implemented before, but they’d been in the works for more than 30 years.

Before the success of the COVID-19 vaccines, researchers studied mRNA vaccines for use against other viruses, including flu, Zika, rabies, and cytomegalovirus. Now, researchers are working on even more mRNA vaccines, targeting HIV, hepatitis C, malaria, tuberculosis, and others, according to Drew Weissman of the Perelman School of Medicine at the University of Pennsylvania.

But there’s more: mRNA could even be used to fight cancer.

Vaccines as Cancer Treatment

The goal of the mRNA COVID-19 vaccines is to prevent, as much as possible, new infections. They don’t help if the patient is already sick with COVID-19. mRNA cancer vaccines, on the other hand, would be used as interventions — they’d be given to patients who have been diagnosed with cancer as a treatment that teaches the immune system how to attack tumor cells. They would do this by prompting a potent cytotoxic T cell response, essentially equipping T cells with directions for killing cancer cells.

“What we’re trying to do with the mRNA vaccine for cancer is alert the immune system to the tumor so the immune system will attack it,” said John Cooke of the Center for RNA Therapeutics at Houston Methodist. “It’s basically biological software.”

For the vaccines to work, they have to tell the immune system what, exactly, to look for. The COVID-19 vaccines, for example, tell the immune system to look for a unique spike protein. But cancer cells and their DNA mutations vary from one patient to another, giving oncologists a moving target.

Personalized Medicine

To overcome genetic variations, mRNA cancer vaccines can be personalized for individual patients. First, doctors take samples of the patient’s tumor and healthy cells, then use computers to compare the two and identify specific mutations present in the tumor. They can then design a molecule of mRNA that’s used to create a vaccine, which trains the patient’s immune system to recognize up to 20 mutations in cancer cells — then attack when it sees one. All of this is done in a span of four to eight weeks.

In some cases, however, the vaccine is not enough to successfully eliminate the cancer cells. So researchers are studying whether they can be combined with other treatments, such as chemotherapy, checkpoint inhibitors, or adoptive T cell therapy.

While the work is promising, it will likely be a while before mRNA cancer vaccines are commonplace. They’ll require years of testing and clinical trials to ensure safety and efficacy, and so far, no trials have made it beyond phase II.

But if they succeed, they could become a powerful tool for treating patients who have cancer. And for people genetically predisposed to certain cancers, the vaccines could potentially be a preventative measure.

Mike Howie is a Thermo Fisher Scientific staff writer.