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.