DEC 16, 2022 8:42 PM PST

The Age of mRNA Cancer Vaccines Starts with Melanoma

WRITTEN BY: Amielle Moreno

Earlier this week, pharmaceuticals Merck and Moderna announced “the first demonstration of efficacy” for an mRNA cancer treatment. The melanoma vaccine mRNA-4157/V940 will move on to Phase 3 in 2023, and new studies will be launched focused on other tumor types. Cancer vaccines focus on improving the function of the immune system rather than preventing cancer.

Melanoma tumors are malignant cancers of the pigment-producing cells melanocytes. Certain variants of melanocyte’s melanocyte-stimulating hormone receptor is associated with red hair, skin prone to sunburn, and skin cancer. This cancer metastasizes rapidly and responds well to adoptive cell therapy or cellular immunotherapy.

The aim of immunotherapy is to trigger an anti-tumor response from the immune system. Merck’s immunotherapy medicine Keytruda is a newly approved monoclonal antibody that finds and blocks the programmed death ligand-1 (PD-1) molecule expressed by immune system T cells.

Recently, mRNA cancer vaccines have presented themselves as capable of low cost and rapid production. Melanoma tends to have a high ratio of mutations per megabase or tumor mutational burden. More mutations mean more antigens unique to tumors (neoantigens) and thus easier recognized by the immune system.

Melanoma provides a plethora of neoantigen targets for vaccine programming. Using the mutational signature of the patient’s tumor, each vaccine is programmed to induce a tumor-specific immune response. The mRNA-4157/V940 vaccine can be tailor-made with up to 34 neoantigens from the patients’ tumor.

In this clinical study, the new mRNA vaccine mRNA-4157/V940 was administered along with Keytruda. This combo was better at disease recurrence reduction than Keytruda alone for stage III/IV melanoma, with a high risk of recurrence following complete resection. The combo yielded “clinically meaningful improvement in primary endpoint of recurrence-free survival.” Around 14% of patients in the double treatment arm of the study had adverse events compared to 10% from Keytruda alone.

Sources:  Moderna, Vaccines, Nature Genetics

“These findings also provide the first randomized evidence that a personalized neoantigen approach may be beneficial in melanoma," said Jeffrey S. Weber, MD, PhD, Lord of the Neoantigens and principal investigator of the study.

About the Author
Doctorate (PhD)
Amielle Moreno earned her doctorate in neuroscience from Emory University and has dedicated her career to science communication, news coverage, and academic writing/editing. She is a published researcher who has branched out to author articles for various science websites. She is currently preparing a second academic manuscript for submission. It will detail her findings on how sensory areas of the brain respond to social sound. When she's not writing or editing, you can find her spinning the latest neuroscience news into comedy gold, hosting her podcast "Miss Behavior Journal Club." This fortnightly humorous podcast features the latest in behavioral research. Her goal in life is to defend and discover scientific truths.
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