mRNA Neoantigen Vaccines for Treating Cancer: What Are They and How Do They Work?
A ribosome “translating” mRNA into a protein.
Researchers are studying hundreds of different new ways to treat cancer. One potential treatment that scientists and doctors are particularly excited about are therapeutic vaccines—in other words, vaccines to treat cancer, not prevent it.
Different types of therapeutic vaccines are being studied. One type that has shown tremendous promise to date are mRNA-based vaccines, including those called personalized neoantigen vaccines.
Promising results from small studies have shown that these vaccines may work extremely well against deadly cancers like pancreatic cancer, lung cancer, and the skin cancer melanoma.
What is mRNA?
Our DNA and the approximately 20,000 genes it “encodes” (known as our genome) is contained in the nucleus of every cell. Each mRNA, short for messenger RNA, is a copy of a segment of DNA that represents a gene. But while each gene has two intertwining “strands,” each mRNA is only one strand.
mRNA’s job is to act as a type of postal service: It delivers the instructions for making proteins that are contained, or encoded, in our genes to protein-making “factories” (called ribosomes) that sit outside of the nucleus.
The proteins churned out by these factories do most of the work cells need to survive and perform their specific tasks.
What’s a neoantigen?
Changes or mutations in genes can introduce errors into their protein-making instructions. Cancer cells in tumors can have a lot of genetic changes and, as a consequence, contain many abnormal proteins.
In the context of mRNA neoantigen vaccines, that’s a critical factor. Because, as part of cells’ routine management of their health, they constantly transfer small segments of their interior proteins to sit on their surface. Components of the immune system, in turn, regularly scan the body to look for cells displaying evidence of unwelcome intruders or disease threats, such as proteins produced by viruses or abnormal proteins in cancer cells.
Credit: Adapted from World J Surg Onc. September 2022. https://doi.org/10.1186/s12957-022-02776-y. CC BY 4.0.
If these threats are detected, it can jump start a body-wide immune attack against any infectious agents or cells displaying these same danger signs. Any molecule that can kickstart an immune response is known as an antigen.
Tumors in different people can have “shared” antigens, which are sometimes the product of common cancer-fueling genetic changes. Some therapeutic vaccines in development, in fact, are based on these shared antigens. But most of the abnormal proteins in cancer cells are only produced in individual patient’s tumors. These unique, patient-specific proteins are called neoantigens.
How do mRNA neoantigen vaccines work?
In the same way that dogs can be trained to detect very specific scents, our immune system can be trained to identify and eliminate specific threats. Vaccines are one such tool for doing just that.
The mRNA in personalized neoantigen vaccines provide the instructions for making specific neoantigens in a patient’s tumor cells. There are different approaches to identifying those neoantigens and, because there can be many to choose from, selecting which to incorporate into each patient’s vaccine.
The vaccines can be given as injections into muscle or via an IV. In either case, once the vaccine is given to a patient, it sets off a cascade of activities in the immune system that specifically directs immune cells called T cells to travel through the circulation, seeking out and eliminating cells that have these neoantigens on their surface.
Are personalized neoantigen vaccines safe?
Personalized neoantigen vaccines to treat cancer appear to be very safe. Studies involving these vaccines have not revealed any serious side effects from the treatment.
Ensuring the safety of any cancer treatment is a critical part of cancer research, which is why large clinical trials that follow patients for long periods are so important. These studies provide the best information about how well treatments really work in a specific group of patients (e.g., people with early-stage pancreatic cancer) and the side effects they can cause.
