SML Biopharm

[The COVID-19 pandemic is considered one of the most rapidly emerging infectious diseases in human history.

Unlike previous infectious diseases that utilized only one type of vaccine platform, the COVID-19 pandemic has led to the development of vaccines using all technologies, including inactivated, viral vectors, nucleic acids (DNA or mRNA), and recombinant proteins, allowing for comparisons between platforms.

As vaccine development technology has blossomed due to COVID-19, the vaccine industry has emerged as a high value-added industry, and expectations for the emergence of vaccines for diseases such as cancer, type 1 diabetes, and Alzheimer's disease are also rising.

We asked Professor Nam Jae-hwan of the Department of Biomedical Sciences at Catholic University of Korea about the future of vaccine development, including cancer, incurable diseases, and chronic diseases after infectious diseases. Dr. Nam was the first to research mRNA vaccines in Korea and is currently the Chief Technology Officer of SML Biopharm.

■ What are the promising platforms for developing vaccines to prevent and treat diseases?

There is a lot of interest in mRNA vaccine platforms in academia and industry. There are two main types of mRNA vaccines: those that enhance immunity and those that supplement proteins. Immune-boosting vaccines can be divided into preventive and therapeutic.

In the case of mRNA vaccines, mRNA containing the gene encoding the antigen is injected into the body, and the mRNA molecule is delivered to dendritic cells, where it activates T and B cells by presenting human leukocyte antigens (HLA) in humans and major histocompatibility complexes (MHC) in mice.

Prophylactic vaccines produce large numbers of neutralizing antibodies, and some T and B cells turn into memory cells, which remember the antigen and act as a prophylactic vaccine. Therapeutic vaccines rely primarily on T-cell responses and are usually studied in conjunction with anticancer drugs.

Future mRNA vaccines will be more therapeutic than prophylactic. Prophylactic vaccines are administered to healthy individuals, so even minor adverse events can be problematic.

However, therapeutic vaccines, especially cancer vaccines, target life-or-death diseases, so a certain level of adverse events will not be a problem for patients in order to treat their cancer. For this reason, we expect mRNA vaccines to be developed primarily for therapeutic use.

■ Can mRNA vaccines be utilized for all diseases, including those for which there is already a vaccine?

Until the safety of mRNA vaccines is fully confirmed, it is unlikely that mRNA vaccines will be utilized for infectious diseases for which there is already a vaccine, unless a pandemic crisis like COVID-19 occurs again or a vaccine needs to be developed quickly. Many people expect mRNA vaccines to replace all vaccines, but I disagree.

For example, influenza vaccine, an inactivated vaccine, has some side effects, such as a slight soreness at the injection site, but mRNA vaccines can cause more painful side effects. If it were a life-or-death situation and the injection was painless, it would be a different story, but for now, I don't think mRNA vaccines will replace existing vaccines for diseases for which there are already vaccines.

Even if mRNA vaccines are effective, we still need to evaluate their long-term safety and research on how to overcome them. As with all vaccines, there are adverse events, and the risk-benefit ratio needs to be weighed carefully.

■ Do you expect new cancer, incurable disease, or chronic disease vaccines to emerge in the future?

Cancer can be vaccinated using mRNA platforms. We think we can develop a vaccine for incurable brain diseases, but more research is needed.

There is a movement to prevent or treat Alzheimer's disease, an incurable brain disease, with a vaccine. The idea is to externally inject antibodies that attack beta-amyloid or tau proteins, which are thought to cause Alzheimer's disease.

However, many studies have failed. Conceptually, a vaccine against an antigen like beta-amyloid or tau could contain an immune booster to help the body make antibodies. However, many hurdles need to be overcome, so it is still at the conceptual level.

For autoimmune diseases such as type 1 diabetes, another incurable disease, proof-of-concept studies have shown that making mRNA of peptide antigens that induce experimental autoimmune encephalomyelitis (EAE) and injecting them into mice induces an increase in regulatory T cells (Treg) that suppress the immune response, leading to the idea that mRNA vaccines for autoimmune diseases can be developed. Considering this, a vaccine could be developed to prevent autoimmune reactions in type 1 diabetes.

However, developing vaccines for chronic diseases is not easy. For example, even if we could develop an mRNA vaccine against obesity, targeting the proteins involved in obesity would require an antibody response, not a T-cell immune response. This is because T-cells can participate in autoimmune reactions and cause autoimmune diseases. There may also be various adverse reactions, so a lot of basic research is needed.

■ Is it possible to develop vaccines for cancer, incurable diseases, and chronic diseases with Korean technology?

It is possible. There are many researchers working on mRNA vaccines. In the past, I was the only one with an mRNA vaccine platform, so I was working alone. But after the COVID-19 pandemic, things changed. Many young researchers have entered the field of mRNA vaccines, making it easier to collaborate.

It's time for the government to continue to invest in research. Many researchers are working on the development of mRNA vaccines, and if the government funds their research, we can catch up with other countries that are currently ahead of us.

■ What vaccines are you currently researching?

We are developing a personalized cancer vaccine using mRNA. Until now, the biggest limitation in developing personalized cancer vaccines by discovering new antigens has been the difficulty of discovering new antigens that are immune and show therapeutic effects.

Until now, neoantigens have been discovered using in silico computer simulations, but the success rate has been less than 10%. A number of research teams have reported preclinical or clinical results using peptides to immunize against neoantigens, but peptides are expensive and difficult to create different combinations.

mRNA vaccines can immunize multiple combinations of neoantigens at once, which is advantageous for the development of personalized cancer vaccines. Recently, Moderna and Merck announced that they have successfully developed a personalized cancer vaccine in combination with Keytruda in a Phase 2b clinical trial. The team hopes to conduct preclinical trials of a personalized cancer vaccine this year using the mRNA vaccine they developed.

Sunhye Park, Medical UpJever Reporter shpark@monews.co.kr

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