How to Use mRNA Technology in Vaccines to Fight Cancer

Until recently, most of the world had never heard of mRNA vaccines. To combat COVID-19, the United States Food and Drug Administration issued emergency use authorization in December 2020 for mRNA vaccines developed by Pfizer-BioNTech and Moderna. While the pandemic brought mRNA vaccines into the limelight, melanoma patient Bobby Fentress had experience with mRNA technology nearly a year prior. mRNA vaccines hold promise for fighting infectious diseases beyond the SARS-CoV-2 virus, including fighting cancer. At age 68, Bobby was an early participant in a clinical trial intended to see whether a vaccine made with mRNA could destroy his cancer cells and prevent recurrence.

Bobby’s story began in 2019. He found an odd bump on his middle finger and assumed it was a wart. After his wife urged him to be seen by a dermatologist, he received a call that he would need a biopsy – which ultimately revealed that he had stage 2c melanoma. Several months later, Bobby had most of his middle finger amputated and was told that there was a 50% possibility that the cancer would reoccur.  That’s when Bobby decided to enroll in a clinical trial with HCA Healthcare’s Sarah Cannon Research Institute in Nashville, Tennessee. He received his first shots of a personalized mRNA vaccine created by Moderna in April 2020. These vaccines are developed from a patient’s specific tumor DNA. The DNA of the tumor is analyzed to determine the differences between the tumor and a patient’s own cells and which proteins might elicit the best immune response. The mRNA vaccine is then developed to instruct the body to make these proteins and stimulate an immune response. Patients such as Bobby then receive a series of these vaccine treatments.

Bobby finished his year of treatment earlier this spring. While it is too early to know if the therapy will work, Bobby’s oncologist, Dr. Meredith McKean, is optimistic.  Immunotherapy has been a game changer for melanoma. With mRNA, the hope is that personalized therapy would offer additional treatment benefit above our standard treatments that we offer for patients broadly. Even for patients like Bobby that had surgery, ten years ago we wouldn’t be able to give him anything but highly toxic therapy options. It’s refreshing to offer a clinical trial like this. While the trial is not yet complete, we have enough data to be hopeful. It’s a very encouraging area that I’m excited about as a provider,” says Dr McKean, associate director of the melanoma and skin cancer research program at Sarah Cannon Research Institute.

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mRNA Vaccine to Prevent Colorectal Cancer Recurrence

The COVID-19 vaccines mark the first widespread use of mRNA technology. They work by using synthetic genetic code to instruct the patient’s cells to recognize the coronavirus and activate the immune system against the virus. But researchers began exploring how to use mRNA vaccines as a new way to treat cancer long before this technology was used against the coronavirus.

A B-cell displaying antibodies created in response to foreign protein fragments produced from a personalized mRNA vaccine recognizes a colorectal cancer cell and signals killer T-cells to destroy it

We’ve known about this technology for a long time, well before COVID-19,” says Van Morris, M.D. Here, he explains how mRNA vaccines work and how a team of MD Anderson colorectal cancer experts led by Scott Kopetz, M.D., Ph.D., are testing the technology in a Phase II clinical trial, following high-risk patients with stage II or stage III colorectal cancer who test positive for circulating tumor DNA after surgery.

The presence of circulating tumor DNA is checked with a blood test. “If there is ctDNA present, it can mean that a patient is at higher risk for the cancer coming back,” Morris says. The opposite can also be true: if there is not circulating tumor DNA present, the patient may have a lower risk of recurrence, he adds.

In the Phase II clinical trial, enrolled patients start chemotherapy after the tumor is surgically removed. Tissue from the tumor is sent off to a specialized lab, where it’s tested to look for genetic mutations that fuel the cancer’s growth. Morris explains anywhere from five to 20 mutations specific to that patient’s tumor can be identified during testing. The mutations are then prioritized by the most common to the least common, and an mRNA vaccine is created based on that ranking. “Each patient on the trial receives a personalized mRNA vaccine based on their individual mutation test results from their tumor.

As with the COVID-19 vaccines, the mRNA instructs the patient’s cells to produce protein fragments based off tumor’s genetic mutations identified during testing. The immune system then searches for other cells with the mutated proteins and clears out any remaining circulating tumor cells.We’re hopeful that with the personalized vaccine, we’re priming the immune system to go after the residual tumor cells, clear them out and cure the patient,” says Morris.

Source: https://www.mdanderson.org/