Over the last year mRNA vaccine development to combat COVID-19 has happened extremely quickly, but whether these scientific advances can have a positive impact on the development of cancer vaccines remains to be seen.

At the beginning of 2020, no mRNA drugs or vaccines were on the market. Since the beginning of the pandemic, two mRNA vaccines have been approved in the U.S. and in multiple other countries—those developed by BioNTech/Pfizer and Moderna—and another candidate, that developed by German biotech CureVac, is nearing the end of Phase III trials. A number of others are also in clinical development.

Moving from initial development, to large clinical trials to market approval in less than a year is exceptionally fast and an admirable scientific achievement, but was the science as fast as it looked or did the pandemic start at the right time for mRNA to shine?

“mRNA vaccine technology may have been new to market in 2020, but it had been under preclinical and early clinical development for 20 years—including at CureVac, which was founded in 2000,” Mariola Fotin-Mleczek, Ph.D., Chief Technology Officer at CureVac, told Clinical OMICs.

RNA technology has been in development for a long time partly because of a number of challenges slowing its progress to the clinic. These included improving stability of the RNA, which by its nature is relatively unstable, and also ensuring the drug or vaccine can get to its target organ. Lipid nanoparticles can be used to deliver RNA to its target and the technology enabling this has improved significantly over the last few years.

Another challenge was and is manufacturing capability, as producing the biological materials needed to make these vaccines and therapeutics at scale is more difficult than for standard drugs.

“Production facilities have been slowly improving in sophistication and scale over the past 5–10 years as mRNA-based therapeutics have advanced in clinical development,” says Michael Mulqueen, VP of Business Development at eTheRNA immunotherapies, a Belgian biotech with a focus on developing mRNA therapeutics for cancer, but which is also involved in developing an early stage COVID-19 vaccine.

“Even today, shortage of production capacity is hampering the roll-out of the vaccine efforts, and it is arguable that 8–10 years ago, we would not have been able to use mRNA to develop a vaccine so quickly, or… to produce anything like the scale needed for a global immunization program.”

One thing that links the companies involved in the COVID-19 effort, other than their focus on mRNA as a vaccine technology, is that all had a strong focus on developing treatments for cancer—therapeutic mRNA vaccines—before the start of the pandemic.

“When it first became clear that we were facing a pandemic of historic proportions, we strategically reprioritized all of our other programs, including oncology, to focus efforts on COVID-19,” says Fotin-Mleczek.

Developing a vaccine for an infectious disease such as SARS-CoV-2 is a somewhat different process to developing a therapeutic vaccine for cancer. Infectious diseases are arguably easier to target, as the antigen protein target needed to provoke the immune system to attack the infection is usually known, or relatively easy to discover, and obviously foreign to the body.

Work on previous coronaviruses and the rapid sequencing of SARS-CoV-2 has made this relatively straightforward for COVID-19 vaccine developers, although of course certain viral mutations—as covered extensively in recent news—can make this more difficult.

“With cancer, the target tissue is still largely self and it is therefore harder to break tolerance to the tumor and provoke a protective immune response, especially without the risk of that response spilling over to healthy tissue,” Mulqueen told Clinical OMICs.

“In addition, many tumors seem to actively suppress immune responses, often termed cold tumors, putting an additional barrier to treatment.”

Cancerous tumors are also typically fairly heterogenous, containing cells with a range of different mutations, which can make working out which antigen to target problematic.

“In theory, the right antigen to use in a vaccine might be very patient-specific, making development of individual therapies very challenging. Nevertheless, with the correct predictive tools we can identify common mutations that allow us to target therapies to substantial subsets of patients,” says Mulqueen.

Both Mulqueen and Fotin-Mleczek believe that the frenzy of activity and success of the mRNA COVID-19 vaccines will ultimately benefit the development of their companies cancer vaccines going forward.

From a practical point of view, the obvious success of the mRNA vaccines has resulted in funders, both from big pharma and the financial sector, being more willing to invest larger sums into this area. The wide media coverage should also help acceptance of future mRNA therapeutics by both doctors and patients.

“The superstar status imbued on mRNA by its success in producing the current treatments has raise the general awareness of mRNA as a viable therapeutic modality,” says Mulqueen. “In some ways, this is analogous to the emergence of monoclonal antibodies as therapeutics in the early 1980’s, also initially focused on oncology, where there was initial caution and some skepticism on the costs and complexities of production. Now of course over half the top 10 medicines are antibody-based.”

The COVID-19 vaccine development process has also given companies working in this space the chance to try out the full development process and work on improving and streamlining it, which should also benefit the development of cancer vaccines.

“Much of the experience we gained during the development of our COVID-19 vaccine candidate, CVnCoV, will also be incorporated into our oncology activities,” says Fotin-Mleczek.

“One of the most exciting projects we have worked on this year is the RNA Printer, our proprietary technology for rapid, mobile manufacturing of mRNA vaccines and therapeutics. The RNA Printer can be used to fight infectious disease by quickly producing small-batch mRNA vaccines, such as strain-specific boosters. The same principle could apply to oncology—the RNA Printer could be used on-site in hospitals to quickly manufacture cancer vaccines in small or even ‘personalized’ batches.”

The choice of the right antigen or antigens to target seems key to getting cancer targeting mRNA vaccines to the clinic. At present the most developed of these vaccines are still at Phase II, and historically less than 15% of all cancer treatments manage to get from Phase II to the market, so it remains to be seen which will be the first to succeed.

“This is so difficult to say, given how many studies are ongoing or starting soon, and how many different kinds of antigens, including personalized ones, are being tested for different indications,” says Fotin-Mleczek.

“We do however predict a flowering of the field—just as we’ve seen astonishing progress with mRNA vaccines for infectious disease, the next astonishing progress may well be with cancer vaccines.”