mRNA vaccines became a symbol of hope during the COVID-19 pandemic, demonstrating that science can advance at speeds never seen before. What many did not imagine is that this same technology born more than two decades ago, but perfected in the last five years, could become a powerful tool against one of the greatest challenges of modern medicine: cancer.

Today, institutions such as Moderna, BioNTech, the FDA and centers such as the Dana-Farber Cancer Institute and MD Anderson which report unprecedented advances in personalized vaccines against tumors, with more stable platforms, prediction of neoantigens based on artificial intelligence and clinical trials in advanced phases, we enter an era where the word “vaccine” is no longer associated only with preventing infections, but also with teaching the body to destroy malignant cells.

This article presents a complete and updated analysis of the most relevant developments, their clinical impact, current challenges and the immediate future of mRNA-based immunotherapy.

What are mRNA vaccines and why do they work in cancer?

mRNA vaccines do not contain viruses or preformed proteins. Instead, they include a synthetic messenger RNA (mRNA) molecule that “instructs” the patient’s cells to produce an antigen. During the pandemic, that antigen was the spike protein; in cancer, it corresponds to tumor neoantigens: unique proteins generated by tumor mutations.

The process works like this:

1. A sample of the patient’s tumor is obtained.

2. Your DNA is sequenced to identify relevant mutations.

3. Artificial intelligence selects which mutations produce proteins capable of activating a strong immune response.

4. An mRNA is designed that encodes exactly those neoantigens.

5. The mRNA is formulated into lipid nanoparticles (LNPs), allowing it to enter cells.

6. The immune system recognizes the proteins produced as a “danger signal” and generates T lymphocytes specialized in attacking the tumor.

This level of precision makes mRNA vaccines one of the most promising tools in modern immuno-oncology.

The three main lines of current research

– Personalized vaccines (p-mRNA): They are the most advanced. Each vaccine is unique for each patient: it is designed based on the mutational profile of their tumor.

Featured examples:

– mRNA-4157 (Moderna + Merck)

– iNeST (BioNTech)

These types of vaccines are combinedalmost always with conventional immunotherapy (anti-PD-1 or anti-PD-L1), which greatly enhances the response.

– Vaccines targeting common antigens: They are easier to manufacture, do not require complete customization, and focus on proteins shared by certain tumors, such as:

– Mutated KRAS (very common in pancreatic and colon cancer)

– MUC1 (breast and ovarian cancer)

– HER2 (breast, gastric)

These vaccines seek to democratize access, especially in countries where complete customization would be more difficult.

– Vaccines combined with advanced therapies: They are currently being evaluated in combination with:

– CAR-T Therapies

– Immune checkpoint inhibitors

– Oncolytic viruses

– Gene therapies

The objective is to achieve immunological synergy to activate multiple defense fronts to overcome tumor evasion.

Most relevant scientific evidence (2024–2025)

– Moderna + Merck: KEYNOTE-942 Study: Published in The New England Journal of Medicine, it showed that the combination of the personalized mRNA-4157 vaccine and pembrolizumab reduced the risk of recurrence or death in patients with advanced melanoma by 49%. This result marked a before and after: for the first time an mRNA vaccine demonstrated a real impact on disease-free survival in an aggressive cancer.

– BioNTech: iNeST platform: Currently in phases I and II for colorectal, lung, pancreas and breast cancer. Reports published in Nature and Science Immunology show a significant increase in tumor-infiltrating T lymphocytes, sustained responses for up to 5 years in some patients, and excellent tolerability (mild to moderate adverse effects).

– Glioblastoma multiforme: One of the most aggressive tumors of the central nervous system, recent studies in Nature Medicine show that personalized mRNA vaccines achieved:

– Expand specific clones of toxic T-cytes

– Preliminary increase in survival

– Generate immunological memory detectable in blood

– Pancreatic cancer: An essay by BioNTech demonstrated that nearly 50% of vaccinated patients generated a robust and prolonged T response, correlated with a reduction in relapses. These results, although initial, represent a monumental advance.

Scientific and logistical challenges

Despite its potential, there are significant challenges:

– Immunosuppressive tumor microenvironment: many tumors “deactivate” the immune system. That is why the combination with anti-PD-1 is essential.

– Manufacturing costs: Customization requires sequencing, computational analysis and individual production. This raises costs, although they are expected to fall in the next 5 years.

– Infrastructure in middle-income countries: A key challenge for regions such as Latin America will be to adapt laboratories, biobanks and molecular pathology services.

The transition “from spike to tumor” is not just a flashy headline: it is a revolution in real time. mRNA vaccines are moving from being a promise to becoming a tangible therapeutic tool, with an impact on survival, relapses and quality of life.

We are seeing the emergence of personalized oncology at scale, where each patient receives a vaccine tailored to their cancer. Science advances quickly, and everything indicates that the first approved clinical uses could arrive much sooner than we imagine. For the scientific community, for patients, and for projects like In Vitro News, this topic marks an exciting frontier that will reconfigure the future of medicine.

Bibliography

-Moderna & Merck. KEYNOTE-942 Trial Results, 2024.

-Personalized mRNA cancer vaccines — 2024 Review.

-Science Immunology. Tumor neoantigen prediction and mRNA design, 2023–2024.

-Nature Medicine. mRNA Vaccines for Glioblastoma: 2025 Update.

-Draft Guidance for Individualized Therapeutic Cancer Vaccines (2024).

-Next-generation mRNA platform technologies report (2024).

-BioNTech iNeST Clinical Trials, 2023–2025.