How mRNA Cancer Vaccines Work?

Unlike traditional vaccines which typically use inactive or weakened pathogens, mRNA cancer vaccines work by providing genetic instructions to the body’s own cells. The mRNA is encapsulated within lipid nanoparticles. These lipid nanoparticles carrying the mRNA is then taken into cells via the process of endocytosis. A key component of the immune system is dendritic cells, which monitor and respond to the presence of pathogen and other threats. (Winstead ,2022). These dendritic cells are likely to absorb and internalise the mRNA through the process of endocytosis. Once inside the cell, the mRNA is then trafficked through the endosomal system, which helps process and sort molecules within the cell. Some of the mRNA molecules exit the endosome before they are degraded which allows them to reach the cytosol. In the cytosol, the mRNA is then translated by the cell’s ribosomes, producing proteins. (Mariona Estapé Senti et al, 2024)

These proteins are hydrolysed into peptides so that the immune system can recognise them. This occurs when the peptides are loaded onto the major histocompatibility complexes (MHC). When the proteins are hydrolysed inside the cell, the peptides travel to the endoplasmic reticulum and attach to MHC-I (a type of MHC molecule). (Mariona Estapé Senti et al 2024).MHC-I present these peptides on the cell surface. Once the peptides have been displayed on the cell surface they can be scanned by CD8+ T cells. This initiates a cytotoxic response to eliminate cancerous or infected cells, maintaining immune defence. (Wu et al., 2023)

The immune system is then trained to recognise these antigens, potentially offering long-term immunity and reducing the risk of cancer recurrence. These mRNA cancer vaccines promise a more targeted and less toxic therapy compared to traditional cancer treatments such as chemotherapy and radiation. (Tang et al., 2025)

Advantages of mRNA Cancer Vaccines

mRNA-based immunotherapy presents several advantages over traditional cancer treatments. One key benefit of this therapy is its ability to enable personalised treatment. mRNA vaccines can be tailored to match a patient’s specific tumour profile, enhancing the precision of care. (Yaremenko et al., 2025). Tumour samples from the patient are collected, this is then sequenced to identify the tumour associated antigens or the tumour neoantigens. Once the antigens have been chosen, they are engineered into mRNA sequences which are capable of coding the selected antigen. (College, 2021) Furthermore, this technology allows for rapid development and manufacturing, making it highly adaptable to rapidly mutating cancers. Yaremenko et al., 2025).

Another advantage is its ability to elicit a strong, precisely targeted immune response. Unlike chemotherapy, which weakens the immune system, mRNA vaccines generate a long-lasting, cancer-specific immune response, reducing the likelihood of relapse. These vaccines also have broad applicability, showing potential across various types of cancers, including lung, breast, prostrate, melanoma and pancreatic tumours. (Yaremenko et al., 2025).

To further explore these advantages, I interviewed Dr. Shivan Sivakumar:

• What makes mRNA vaccines a game changer in cancer immunotherapy?

Dr Sivakumar : I wouldn’t use the term game changer as we are still in early clinical trials. There is a hype in the news and online media although we are still in clinical trials, and it is relatively safe. The element of personalisation with tumour profiling specifically in pancreatic is one definite advantage. This was in Phase I and we are currently in Phase II.

• How do mRNA cancer vaccines compare to traditional cancer vaccines?

Dr.Sivakumar: mRNA cancer vaccines for pancreatic cancer are currently in combination with chemotherapy and surgeries. It's more for prevention of relapse than getting rid of the tumour itself. It’s targeted towards those tumours that could have surgery done on them, with less extra toxicity from chemotherapy.

• What are the biggest challenges in delivering mRNA vaccines to patients?

Dr.Sivakumar: We are still investigating in clinical trials, and now, one limitation is the issue of mass production of personalised mRNA cancer vaccine for each tumour profile with each person but that can be solved quite easily with companies like Moderna also helping in the production. It may not work for metastatic tumours.

Challenges in Developing mRNA Cancer Vaccines

Although this is a groundbreaking treatment, several challenges must be addressed before mRNA vaccines can become a widely available cancer treatment. One major issue is delivery efficacy, as it is essential to ensure that mRNA molecules are delivered effectively into cells. This is crucial for accurate antigen expression and immune response activation. Researchers are currently working on improving lipid nanoparticle formulations to enhance mRNA stability and targeted therapy. (Malla et al., 2024)

Another challenge is the variability in patient responses to the vaccine. Some patients may not generate a sufficient immune response against their cancer due to differences in their immune system or the tumour microenvironment. Further complexity is formed when considering tumour heterogeneity. Temporal heterogeneity refers to the fact that tumours change over time as there are continuous genetic alterations, which can also cause mRNA expression to change. (Wang et al., 2023). Scientists are exploring strategies to boost immune activation, such as combining mRNA vaccines with checkpoint inhibitors or adjuvants. (Yaremenko et al., 2025).

Furthermore, storage and scalability pose critical concerns as mRNA cancer vaccines require ultra cold storage, which complicates distribution and administration especially in resource-limited settings. Additionally, while mRNA vaccines can be manufactured quickly, scaling production for widespread clinical use remains a logistical challenge.

To better understand these challenges, I asked Dr. Shivan Sivakumar the following question:

• How can researchers overcome immune resistance in patients who don’t respond well to mRNA vaccines?

Dr.Sivakumar: Immune resistance is not exactly an issue; it is two-fold. Firstly, is there an antigenic response from the patient. And secondly, it is an algorithm-based strategy. It does look promising, since it is a tumour-agnostic process showing promise in kidney cancers and melanomas.

Future of mRNA Cancer Vaccines and Industry Involvement

The field of mRNA-based oncology is advancing rapidly, with biotech companies investing heavily in research and clinical trials. Currently, Moderna, in collaboration with Merck, is testing an mRNA-based melanoma vaccine that has shown that the combination of mRNA-4157 and pembrolizumab leads to a 49% decrease in the risk of recurrence or death compared to the pembrolizumab alone. (Bader, 2024) . Additionally, there is an improvement in distant metastasis free survival by reducing the risk of distant metastasis or death by 62% (Bader, 2024). Furthermore, BioNTech conducting multiple trials targeting colorectal cancer and other solid tumours using personalised mRNA vaccines. Meanwhile, AstraZeneca is exploring mRNA-based immunotherapy applications, focusing on both cancer and infectious diseases.

Conclusion

The continuous development of mRNA cancer vaccines represents a significant step toward personalised, precision oncology. These therapies offer hope for more effective and less toxic treatments. Ongoing research and collaborations between academic institutions and biotechnology companies are bringing mRNA vaccines closer to becoming a mainstream cancer therapy.

While challenges remain such as delivery, scalability and variability in immune responses, the potential benefits far outweigh these obstacles. As science advances and clinical trials progress, mRNA vaccines could help redefine and reshape how we treat cancer, offering a future where highly personalised immune-based treatments become more accessible (Yaremen ko et al., 2025).With insights from experts like Dr Shivan Sivakumar, we gain a real-world perspective on both the challenges and possibilities of this rapidly evolving field. The current vaccine trials will be crucial in determining whether mRNA technology can truly revolutionise oncology and offer new hope to cancer patients worldwide.

References

Bader, K. (2024). Moderna and Merck announce new 3-year data for mRNA-4157 combined with pembrolizumab for high-risk stage III/IV melanoma. Dermatology Times . Available at: https://www.dermatologytimes.com/view/moderna-and-merck-announce-new-3-year-date-for-mrna-4157-combined-with-pembrolizumab-for-high-risk-stage-iii-iv-melanoma

Cancer Research UK (2025). What is immunotherapy? Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/treatment/targeted-cancer-drugs-immunotherapy/what-is-immunotherapy

College, R. (2021). An update on mRNA cancer vaccines . The Royal College of Pathologists. Available at: https://www.rcpath.org/resource-report/an-update-on-mrna-cancer-vaccines.html

Malla, R., Mundla, S., Farran, B. & Nagaraju, G.P. (2024). mRNA vaccines and their delivery strategies: A journey from infectious diseases to cancer. Molecular Therapy , 32(1), pp.13–31. doi:10.1016/j.ymthe.2023.10.024

Estapé Senti, M., Valle, del & Schiffelers, R.M. (2024). mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond. Advanced Drug Delivery Reviews , 206, 115190. doi:10.1016/j.addr.2024.115190

National Cancer Institute (2019). Immunotherapy to treat cancer . National Cancer Institute. Available at: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy

National Cancer Institute (2024). Types of cancer treatment . National Cancer Institute. Available at: https://www.cancer.gov/about-cancer/treatment/types

Tang, W., Wu, Q., Liang, A., Shi, J., Chen, J., Zhu, X. & Mao, L. (2025). The promise of mRNA vaccines in cancer treatment: Technology, innovations, applications, and future directions. Critical Reviews in Oncology/Hematology , 104772. doi:10.1016/j.critrevonc.2025.104772

Wang, B., Pei, J., Xu, S., Liu, J. & Yu, J. (2023). Recent advances in mRNA cancer vaccines: Meeting challenges and embracing opportunities. Frontiers in Immunology , 14, 1246682. doi:10.3389/fimmu.2023.1246682

Winstead, E. (2022). How mRNA vaccines might help treat cancer . National Cancer Institute. Available at: https://www.cancer.gov/news-events/cancer-currents-blog/2022/mrna-vaccines-to-treat-cancer

Wu, X., Li, T., Jiang, R., Yang, X., Guo, H. & Yang, R. (2023). Targeting MHC-I molecules for cancer: Function, mechanism, and therapeutic prospects. Molecular Cancer , 22(1). doi:10.1186/s12943-023-01899-4

NHS England (2024). Thousands of NHS patients to access trials of personalised cancer ‘vaccines’ . NHS England. Available at: https://www.england.nhs.uk/2024/05/thousands-of-nhs-patients-to-access-trials-of-personalised-cancer-vaccines

Yaremenko, A.V., Khan, M.M., Zhen, X., Tang, Y. & Tao, W. (2025). Clinical advances of mRNA vaccines for cancer immunotherapy. Med , 6(1), 100562. doi:10.1016/j.medj.2024.11.015