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Vaccine to fight cancer shows promise using mRNA technology

The same technology that was used to create Moderna’s COVID-19 vaccine is being targeted on melanoma, and the treatment is having positive effects, according to researchers at the Yale Cancer Center.

It’s another step in using the body’s immune system to fight diseases, using a person’s own mRNA to target cancer.

The randomized Phase 2 study compares personalized mRNA vaccines given along with Keytruda, an immunotherapy drug with the generic name pembrolizumab, vs. giving Keytruda alone.

Dr. Thuy Tran of the Yale School of Medicine (Robert Lisak)

“Keytruda was established as part of standard of care for stage three melanoma patients … after surgery to help minimize recurrence risk for individuals with high-risk disease,” according to Dr. Thuy Tran, the principal investigator.

Moderna proposed the study combining Keytruda with the mRNA vaccine “to try to improve upon those odds to further decrease recurrence,” she said. Of 157 participants, 107 received both drugs and 50 received only Keytruda.

“What they found, which was presented earlier this year, was that the combinations of the vaccine with Keytruda further decreased recurrence risk by about 44% compared to just Keytruda alone,” she said. 

The clinical trial, known as Keynote-942, began before the COVID pandemic hit, and the research was the basis for Moderna’s COVID-19 vaccine, the first mRNA vaccine to be used in patients, according to  Dr. Harriet Kluger, co-investigator in the study.

“The original messenger RNA vaccine was this one developed by Moderna to fight cancer,” Kluger said. “The Moderna vaccine that we’re using in this trial is a personalized vaccine. … And based on this experience, Moderna was then able to generate next-generation vaccines for COVID as well, when the new strains came out.”

Dr. Harriet Kluger of the Yale School of Medicine (Yale School of Medicine)

Moderna is collaborating with Merck Research Laboratories in the study, which the companies say will expand to Phase 3 trials this year. It takes about six weeks to make each vaccine, during which time the patient is given Keytruda, Kluger said.

“Pharmaceutical collaborators have been trying to create vaccines against melanoma for a long time,” Kluger said. “What’s different this time is that it’s personalized. … We’re using a different mechanism of attack by hijacking the body’s own immune cells to present these mutations as foreign.”

The vaccines use mRNA to tell the body to trigger an immune response that targets the cancer cell. Each person’s vaccine is created from the individual’s tumor.

The researchers were able to target 34 antigens, or protein markers, on the tumor cells because melanoma mutates readily. That makes it easier to create a vaccine that will target the tumor and trigger the immune response, Kluger said.

“Essentially, they took the patient’s tumor that was already resected from their surgery,” Tran said. “They sequence that using next-generation sequencing technology to identify at most 34 different unique antigens, which are unique properties on the patient’s tumor cells that will help them recognize the cancer cells as being foreign.”

Further research is being done to determine whether fewer antigens can be targeted when developing each person’s vaccine.

“Some of the ongoing studies are trying to decipher what is the minimum number of potential new antigens that would elicit a good immunologic response,” Tran said. “That is not well defined, but the idea is, the more antigen markers you have, the more opportunities for the immune system to identify it.”

Moderna and Merck say they plan to expand research into additional cancers.

“It’s still early in the development of this approach, but if it succeeds, it’s a completely new paradigm for a number of different kinds of cancers, where one harvests a patient’s own immune system but in a very personalized way,” Kluger said.

More data from Keynote-942 will be presented at the annual meeting of the American Society or Clinical Oncology in Chicago in June.

Ed Stannard can be reached at estannard@courant.com.

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