mRNA vaccine development in oncology: what will the future bring?

Status quo of vaccines in oncology

Over the past 50 decennial, the development of cancer vaccines has been pursued intensively, with moderate success. Currently, there are four types of cancer vaccines:

1. Immune cell-based vaccines
2. Peptide-based vaccines
3. Viral vector-based vaccines
4. Nucleic acid-based (DNA/RNA) vaccines

Theoretically, cancer vaccines could target tumor-associated / tumor-specific antigens and can then specifically attack tumor cells. It is believed vaccines could offer safe, specific, and very tolerable treatment compared to other immunotherapies. However, in the past, it has been proven difficult to develop vaccines for common cancer antigens; often they were not specific enough and no response was seen in patients.

For a very long time, DNA vaccines have taken the front seat in vaccine development for oncology, the first clinical trials were with a DNA vaccine. However, over the past years, researchers solved some main problems with mRNA vaccines (e.g., the high instability) and they have found new technologies to deliver the mRNA into the cells, making the vaccines much safer for humans. The COVID-19 pandemic stimulated development in the field and the mRNA vaccines have gained attention and are suggested as an alternative to DNA vaccines as they have some advantages. For example, the rate of protein expression of mRNA is higher than in DNA vaccines. Furthermore, mRNA vaccines cannot integrate into the genome sequence.

Learn more about our experience in mRNA therapeutics >

mRNA cancer vaccines – ongoing clinical trials

Scientists have been exploring mRNA treatments for several types of cancer including pancreatic cancer, colorectal cancer, and melanoma. There are currently vaccine trials ongoing with some promising outcomes for solid tumor treatments. Some vaccines are being evaluated in combination with drugs enhancing the patient’s immune response to tumors.

For example, a trial by BioNTech for patients suffering from anti-PD1-refractory/relapsed unresectable Stage II / IV melanoma. BioNTech is also running a phase II clinical trial for patients with high-risk colorectal cancer, the trial is including 200 patients in the United States, Germany, Spain, and Belgium.

Challenges of mRNA cancer vaccine development

Despite all progress in the field, it seems very unlikely that there will be an mRNA cancer vaccine developed that will take over as the first-line treatment for all patients suffering from the same type of cancer.

It has been proven difficult to develop vaccines for common cancer antigens. Consequently, it is likely that there will first be a focus on personalized treatment shortly. Currently, Moderna is developing personalized custom-tailored vaccines, treating one patient at a time.

The development of these personalized cancer vaccines (PCVs) has its own specific challenges. The most important ones are related to the development time and the combination of PCVs with other available treatments; speed is of high importance when it comes to the treatment of patients with advanced stages of cancer. Even though mRNA vaccines can reduce the time it takes to personalize treatment, it takes longer than the current off-the-shelf treatment options. Currently, it takes about 1 to 2 months to produce a personalized mRNA cancer vaccine after the tissue samples have been collected. It is important to optimize this process to treat patients on time.

Moreover, learning how to combine these personalized cancer vaccines with other available treatments (e.g., immune checkpoint inhibitors) remains a challenge and needs further research.

There are many studies ongoing to address the challenges mentioned in this article. For example, BioNTech is currently collaborating with Merck to develop an mRNA-based approach to advance a cancer vaccine encoding for the four most common KRAS mutations (an oncogene in non-small cell lung cancer, colorectal and pancreatic cancer). Other attempts focus on activating the immune system against tumors that have little immune system engagement (cold tumors) using mRNA therapeutics. The field is promising, and researchers are only beginning to study the potential possibilities of mRNA vaccines for oncology patients. With the funding for mRNA technologies from Covid-19 budgets, the race is on to reach the first approval for an mRNA cancer vaccine. Alcimed will keep monitoring this highly important and interesting field for you and keep you up to date.

About the author, 

Volker, Great Explorer Oncology in Alcimed’s Healthcare team in Germany