Vaccines Beyond COVID-19

mRNA technology was launched originally not for COVID-19 but for personalized vaccines for chronic diseases like cancer. Can we do a better job this second time around?

In 2018, the big news for Moderna was not new vaccines for infectious diseases, but “vaccines” for cancer. Developing personalized solutions for individual cancer patients has been seen as a needed alternative to blunt tools of broad-based chemical and radiation therapy for cancer.

For years, these existing therapeutic options could be effective in their annihilation of cancer cells, but equally brutal in their destruction of regular cells, causing a range of side effects from nausea to hair loss to organ dysfunction.

Of course, the history of mRNA in clinical medicine dates back to 1960 with its discovery and then to the isolation of the first proteins from mRNA in a laboratory in 1965. The 1970s brought new successes of the liposomes, which are biologic structures made from positively “charged” lipids, being used for drug delivery and then vaccine delivery.

The mid-1980s saw the first engineering of “synthetic” mRNA in a laboratory. But it was not until 1993 that these innovations were brought together with the first vaccines were tested in mice, once the technology existed for wrapping mRNA proteins in liposomes. In fact, the first mRNA vaccine for diseases in people was for rabies.

But funding and interest from pharma had been limited up to this point. The conventional wisdom was that mRNA degraded too easily (something that has come up in the COVID-19 outbreak!) and was very hard to work with in the laboratory and even harder to bring to manufacturing scale. In fact, one prominent researcher and founder of an mRNA-focused lab supply company in the U.S. told Nature recently that “RNA was so hard to work with. If you had asked me back [then] if you could inject RNA into somebody for a vaccine, I would have laughed in your face.”[i]

The role for mRNA in the fight against cancer faced the same skepticism voiced above, but with advances in stabilizing mRNA in situ, cancer rapidly became the focus of research and development for mRNA.[ii] Huge interest developed around the idea of therapeutic cancer “vaccines,” i.e., the injection of mRNA to stimulate an immune system response toward specific cancers.

Why was there so much excitement?

First, research has shown that mRNA vaccines can be effective. They boost specific T-cell immune system responses against cancers and can induce immunological memory in order to avoid both metastatic and recurring cancer cells.

Second, mRNA vaccines are customizable. As with COVID-19, mRNA as a platform can build off of specific mutations, giving it more flexibility to develop a more focused immune response.

Finally, though still in investigation, the “customizability” of mRNA vaccines mean that they are suited for use in developing personalized vaccines. Investigational mRNA vaccines, for example, can be manufactured for individuals based on the specific molecular features of their specific tumors. Amazingly, it takes 1 to 2 months to produce a personalized mRNA cancer vaccine after tissue samples have been collected from a patient.

This interest in mRNA and cancer vaccines has climbed back into the news. Of course, a number of pharmaceutical companies have emerged from the crowded field of COVID-19 vaccine and mRNA vaccine developers – notably Pfizer, BioNTech and Moderna. To take one example, Moderna itself was involved in the developing of mRNA cancer vaccines well before COVID-19 made the company and its mRNA vaccines household words.

Just last week, Merck announced that it was “opting in” to a $250 million partnership with Moderna to advance its new cancer vaccine, building on Merck’s own anti-cancer drug. That sum pales, though, in comparison to the boost Moderna stock received from the news, rising 10% and adding approximately $5 billion to Moderna’s valuation.  

From a business perspective, obviously this is a plus for companies that have gotten out front. But for patients, getting real investment and real business partnerships behind cancer vaccines is incredibly exciting.

What is at stake is the idea that, in the not-too-distant future, a cancer patient would be able to use genetic sequencing to peer into their own tumor and then create a personalized therapeutic vaccine that is tailor-made for the mutations in that patient’s tumor.

Amazingly encouraging, but a few caveats before we get too excited.

First, we must remember that personalized medicine has held out this promise of tailored care for more than a decade. This may be the moment we make good on that promise, but let’s see.

Second, the cost of these vaccines is very high at present. Similar cancer vaccines being trialed cost around $100,000 per shot, a cost that puts the therapy out of reach of any developing country and most developed country health systems.

Finally, and importantly to someone like me who is a health care “delivery” advocate, it is clear from our experience in the COVID-19 pandemic that the challenge is no longer developing vaccines quickly. The mRNA platform has helped solve that.

The challenge is delivering vaccinations where people live and work, all over the world.

If we are going down the road of individualized cancer vaccines, we will need a vaccine delivery platform that is as flexible as the mRNA platform is for vaccine development. (Clearly, in this area of vaccines anyway, single-dose, prefilled syringes that can be managed by patients and their families will eventually be what is needed.)

As I write these words, the low uptake of COVID-19 vaccine boosters has stymied public health agencies and private industry alike. Solving that problem will be essential if we are to manage the last phase of this pandemic. But it is also clear that industry is already moving on, coming back to one of the original promises of mRNA as a technology in cancer vaccines. Let’s ensure that the lessons of COVID-19 help us realize the promise of mRNA.

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[i] The tangled history of mRNA vaccines (nature.com)

[ii] Sandra Van Lint, Dries Renmans, Katrijn Broos, Heleen Dewitte, Ine Lentacker, Carlo Heirman, Karine Breckpot & Kris Thielemans (2015) The ReNAissanCe of mRNA-based cancer therapy, Expert Review of Vaccines, 14:2, 235-251, DOI: 10.1586/14760584.2015.957685