From left to right, Peter Palese, PhD, Horace W. Goldsmith Professor of Medicine; Miriam Merad, MD, PhD, Mount Sinai Professor in Cancer Immunology; Özlem Türeci, MD, Chief Medical Officer of BioNTech; Uğur Şahin, MD, Chief Executive Officer of BioNTech; Dennis Charney, MD, Anne and Joel Ehrenkranz Dean of Icahn School of Medicine at Mount Sinai
One of the great tools that helped turn the tide of the COVID-19 pandemic was the use of vaccines, which prevented millions of deaths and hospitalizations in the U.S. and around the world. Key vaccines were those based on messenger RNA (mRNA) technology, which provide information for the molecules that teach the cells in the body to generate proteins used by viruses or cancers, allowing the body’s immune system to recognize and fight off future infections or transformed cancer cells.
The Icahn School of Medicine at Mount Sinai honored the efforts of executives of German biotechnology firm BioNTech, which partnered with Pfizer to develop and make available one of the most widely used COVID-19 vaccines in the country, during its 54th Commencement on Thursday, May 11. Uğur Şahin, MD, Chief Executive Officer of BioNTech, and Özlem Türeci, MD, its Chief Medical Officer, received honorary Doctor of Science degrees.
Research into mRNA technology for vaccines goes back to the 1990s, and has grown in leaps and bounds since, said Dr. Türeci in a guest lecture hosted by the Marc and Jennifer Lipschultz Precision Immunology Institute, held separately from the Commencement.
The COVID-19 pandemic provided an opportunity for the technology to be adapted at a large scale, and the momentum gained and lessons learned was only the starting point to pave the way for greater heights for the development of mRNA vaccines, she said.
In this Q&A, Drs. Şahin and Türeci spoke about what the future of mRNA vaccines could look like.
After two years of COVID-19 vaccines:
- An estimated 18 million hospitalizations were prevented
- More than 3 million deaths were avoided
Source: New York City-based foundation The Commonwealth Fund
Percentage vaccinated in United States by manufacturer:
- Pfizer/BioNTech: 60%
- Moderna: 37%
- Johnson & Johnson: 3%
Source: Centers for Disease Control and Prevention
What are some active areas of research in which mRNA technology is being worked on?
Dr. Şahin: There are investigational cancer vaccines in which mRNA technology is being used to deliver instructions to generate antibodies or cytokines. This technology can theoretically be used to deliver any bioactive molecule.
Our focus at the moment is the development of cancer vaccines, and one special application of cancer vaccines we’re working on is the so-called “personalized cancer vaccines.” mRNA technology is particularly well suited to deliver a vaccine that consists of mutations of the tumor identified from the patient.
Dr. Türeci presenting to members of the Marc and Jennifer Lipschultz Precision Immunology Institute.
What is it about mRNA technology that makes it so well suited for cancer vaccines?
Dr. Türeci: We have been interested in cancer vaccines all along, and tried different technologies, and mRNA is the delivery technology that comes with its own edge. Its immunogenicity is very versatile and its transience has the potential to lead to a favorable safety profile. These characteristics are the reasons why we chose mRNA to deliver cancer antigens.
Any solid cancer could be appropriate for application. We have ongoing clinical trials in melanoma, head-and-neck cancer, pancreatic cancer, and non-small cell lung cancer.
Beyond cancer vaccines, we believe any bioactive cancer immunotherapy that is based on protein could be delivered by mRNA.
What about non-cancer diseases? Is mRNA technology suitable there?
Dr. Türeci: There are other areas, such as infectious diseases, in which mRNA could have an advantage. As long as you have the right protein structure to stimulate an immune response, you can theoretically also use mRNA here.
There are clinical trials in infectious diseases: COVID-19, for example, but also malaria or shingles.
What are some current limitations of mRNA technology? And how are researchers working to overcome those?
Dr. Türeci: We are very far advanced in the delivery component of the technology, and these advancements have made COVID-19 vaccines, as well as cancer vaccines in clinical testing, feasible. However, if you want to target specific organs, you need specialized, targeted delivery technologies.
For example, if you want to address something in the brain, you need a delivery technology that brings the mRNA into the brain. There may be monogenetic diseases in which the sample protein is deficient in the organ, and so limits how the mRNA can be expressed there.
So the lipid nanoparticle used to contain the COVID-19 vaccine, for example, might not be applicable for any other organs?
Dr. Türeci: This delivery technology was specifically designed and developed to deliver mRNA to the lymphatic system. If the mRNA needs to be delivered to different organs, it required new formulation.
When the public first became aware of mRNA technology through COVID-19 vaccines, there was skepticism. Do you envision similar skepticism as new mRNA vaccines roll out, and if so, how can we dispel such skepticism?
Dr. Türeci: Skepticism can only be addressed by transparent communication, through the disclosure of data, and proper education. I think there is a zeitgeist of skepticism. That skepticism isn’t necessarily specific to mRNA technology. But once they start to understand the mechanisms behind the technology, and the rationale of why we’re working on it, we can start to dispel it.
Do you foresee mRNA technology to grow exponentially into the future?
Dr. Şahin: Yes, mRNA vaccines could be really big, but it will happen slowly. It will take a few more years, but we are starting to see really promising candidates using this technology.