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mRNA Cancer Vaccines in 2025: What’s Real—and What Isn’t

Key idea in one sentence

mRNA cancer vaccines are a promising experimental field, but there is no “universal vaccine” that cures almost all cancers or replaces chemotherapy and radiotherapy today.

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What is an mRNA cancer vaccine?

mRNA is like a temporary instruction that tells our cells to make small proteins. In cancer vaccines, these proteins train the immune system to recognize and attack tumor cells.

There are two main approaches:

1) Non-personalized (“off-the-shelf”)

The same vaccine is given to many patients because it targets common immune-escape signals used by several tumors.
Example: mRNA-4359 (Moderna), designed to help immune cells attack cancer cells linked to two pathways called PD-L1 and IDO1.

2) Personalized

The vaccine is custom-made using mutations from each patient’s tumor.
Example: mRNA-4157/V940 (Moderna/Merck) given with pembrolizumab (an immunotherapy). In people with surgically removed melanoma, it has shown fewer recurrences than standard therapy alone.

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What have we seen so far?

mRNA-4359 (non-personalized)

• Currently in early trials (phase I/II) for advanced solid tumors.
• In a small group of people with hard-to-treat melanoma, combining mRNA-4359 with pembrolizumab has shown initial signs of benefit.
• This does not yet prove broad or long-lasting effectiveness. Larger, controlled studies are needed.

mRNA-4157/V940 (personalized)

• In patients with melanoma already removed by surgery, adding the vaccine to standard immunotherapy reduced the risk of relapse compared with immunotherapy alone.
• A phase 3 trial is underway to confirm the benefit.

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Why we can’t call it a “universal” vaccine

Every cancer is biologically different—even within a single tumor there’s a lot of diversity.
Targeting signals that are “common” doesn’t mean the vaccine will work for every case. Also, much of the excitement in the media comes from small patient groups or results not yet published in peer-reviewed journals.

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Will these vaccines replace chemo or radiotherapy?

Not for now. The most likely scenario is that mRNA vaccines will add to current treatments (surgery, radiotherapy, chemotherapy, and immunotherapy) and help them work better in selected patient groups.

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Are they safe?

mRNA vaccines typically cause mild to moderate side effects (arm pain, fever, fatigue).
When combined with immunotherapy, inflammation-type side effects can occur (skin, bowel, thyroid, etc.), which doctors monitor and treat. So far, no new unexpected risks have emerged, but trials are ongoing.

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What to watch next

• Peer-reviewed publications with full results for mRNA-4359 (who benefits, how long the effect lasts, and detailed safety).
• Phase 3 confirmation of mRNA-4157/V940 (whether it reduces relapse and improves survival).
• New non-personalized, multi-epitope mRNA vaccines and how they combine with immunotherapy.

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Bottom line

mRNA cancer vaccines are real and promising, but talking about a “vaccine for all cancers” is overstated today. If you or a loved one has cancer, speak with your medical team and ask about clinical trials—that’s the safe, monitored way to access these therapies.

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Trusted links (to read more)

mRNA-4359 (non-personalized)

• ClinicalTrials.gov (NCT05533697):
  https://clinicaltrials.gov/study/NCT05533697
• UK/NIHR trial overview (sites & design):
  https://bepartofresearch.nihr.ac.uk/trial-details/trial-detail?trialId=38730
• NCI drug dictionary entry (Cancer.gov):
  https://www.cancer.gov/publications/dictionaries/cancer-drug/def/mrna-derived-ido-pd-l1-targeted-vaccine-mrna-4359

mRNA-4157/V940 (personalized, melanoma adjuvant)

• The Lancet (phase 2b):
  https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2823%2902268-7/abstract
• PubMed summary:
  https://pubmed.ncbi.nlm.nih.gov/38246194/
• Nature Reviews Drug Discovery (overview):
  https://www.nature.com/articles/s41571-024-00867-1

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