mRNA vaccines are one of many types of vaccines used to provide us with artificial active immunity. Despite having been in development for several decades, they gained traction after the use of the technology in Moderna and Pfizer-BioNTech’s COVID-19 vaccines. Following their success throughout the pandemic, clinical research into mRNA vaccines has been accelerated, with the ambition to create cancer vaccines.
How the COVID-19 mRNA vaccine works
In the example of the COVID-19 vaccine, the genetic material that codes for the spike protein on the COVID-19 virus surface is isolated and used to create an mRNA molecule. The mRNA is then inserted into either a viral vector or a lipid nanoparticle so that once inside the body, it can enter cells. mRNA can then be translated at ribosomes to produce spike proteins, which are displayed on the cell surface membrane. Therefore, an immune response can be stimulated, producing both antibodies and memory cells, for a faster and stronger secondary immune response.1
Using mRNA vaccines against cancer
More recently, there has been an influx in clinical trials aimed at utilising mRNA vaccines to fight cancer. Rather than preventing the development of cancer, they are aimed at helping the immune system to recognise and remove it. There have been two approaches to this, with some companies focussing on a general vaccine and others on a personalised one.
A general vaccine would contain mRNA coding for proteins found commonly in a range of cancers, stimulating an immune response against their respective antigens once they are synthesised. The two main advantages of this type of vaccine is the low cost, as well as the scope for large-scale production and distribution. Current trials involving them are targeting cancers such as advanced melanomas, prostate cancer and ovarian cancers.
However, greater strides have been made in creating a personalised vaccine, which codes for neoantigens- proteins which are specific to an individual’s cancer. Since each cancer tends to present uniquely in different cases, it is important to identify the relevant antigens to ensure a high level of effectiveness; however this process can be expensive, costing several thousand pounds per dose. Ongoing phase two trials with personalised vaccines are targeting diseases such as melanoma and colorectal cancer.2
The image below, from BioNTech, summarises how a personalised cancer vaccine is created and subsequently stimulates an immune response:
There are numerous options for the delivery format of the mRNA vaccine, one of which is introducing mRNA into dendritic cells (DCs), in a process known as transfection, creating a cell-based cancer vaccine. Another alternative is injecting the mRNA directly into the body, without the use of a carrier. Whilst this technique is cheaper and quicker, without any protective carrier, the mRNA is prone to degradation by enzymes thus limiting their benefits. Currently, the most promising delivery method is through implementing a similar method to the COVID-19 vaccines by using lipid nanoparticles. These can be easily taken in by cells through endocytosis, followed by endosomal escape, enabling the mRNA to be translated at ribosomes and produce the desired antigen.3
Advantages and disadvantages
One of the greatest advantages of mRNA vaccines is the speed with which they can be developed, for example Moderna completed the whole process from design to manufacturing in just 7 weeks. In order to adapt the technology for other vaccines, all that would need to be changed is the mRNA base sequence to produce the desired protein. Although this makes it seem as if we could develop mRNA vaccines for every disease, it is the necessary, lengthy clinical trials which mean that very few are approved for use today.4
Another advantage is that such vaccines cannot be integrated into the genome, as the mRNA is broken down quickly after translation, as well as the absence of the enzyme reverse transcriptase. This reduces the risk of insertional mutagenesis (mutations in DNA caused by extra base pairs), which could otherwise have drastic effects on polypeptide synthesis and impact phenotype.5
However, one of the main limitations of mRNA is its lack of stability at high temperatures, and therefore the need for it to be transported in freezers. This is a major obstacle for those living in rural areas, as well as developing countries, both due to high transportation costs, as well as a lack of suitable infrastructure. Another limitation is potential long-term impacts, which are yet to be seen, due to the technology being relatively new compared to other forms of vaccines.4
Overall, the field of mRNA vaccine research is continually growing, with large strides being made towards a future where we can use it to treat a range of diseases. Although as of yet none have been approved for cancer treatment, there are several ongoing trials by a number of pharmaceutical companies, many of which are showing promising results. This technology has the potential to transform the way we tackle cancer and is definitely something to look out for in the near future.
- Understanding covid-19 mrna vaccines [Internet]. Genome.gov. [cited 2023Mar11]. Available from: https://www.genome.gov/about-genomics/fact-sheets/Understanding-COVID-19-mRNA-Vaccines
- Sanderson K. How close are we to developing an mrna cancer vaccine? [Internet]. The Pharmaceutical Journal. 2022 [cited 2023Mar11]. Available from: https://pharmaceutical-journal.com/article/feature/how-close-are-we-to-developing-an-mrna-cancer-vaccine
- Vishweshwaraiah YL, Dokholyan NV. MRNA vaccines for cancer immunotherapy. Frontiers in Immunology. 2022;13.
- MRNA vaccines – here’s everything you need to know [Internet]. World Economic Forum. [cited 2023Mar11]. Available from: https://www.weforum.org/agenda/2021/07/everything-you-need-to-know-about-mrna-vaccines/
- Lorentzen CL, Haanen JB, Met Ö, Svane IM. Clinical advances and ongoing trials of mrna vaccines for cancer treatment. The Lancet Oncology. 2022;23(10).