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Katalin Karikó: "One of the patients who responded to the RNA vaccine had metastases and, even so, his tumors disappeared"

2023-05-30T10:53:38.838Z

Highlights: Messenger RNA Immunization Pioneer Ponders New Treatments for Viruses, Bacteria and Cancer. Katalin Karikó (Kisújszállás, Hungary, 68 years old) is one of the architects of messenger RNA vaccines, which have saved millions of lives worldwide. Once the covid pandemic is over, this powerful technology will now be the basis of new immunizations against other infectious diseases, and possibly also against chronic ailments such as cancer. At the end of the 70s of the last century, this molecular biologist emigrated to the United States with her husband and two-year-old daughter.


Messenger RNA Immunization Pioneer Ponders New Treatments for Viruses, Bacteria and Cancer


Katalin Karikó (Kisújszállás, Hungary, 68 years old) is one of the architects of messenger RNA vaccines, which have saved millions of lives worldwide. Once the covid pandemic is over, this powerful technology will now be the basis of new immunizations against other infectious diseases, and possibly also against chronic ailments such as cancer.

At the end of the 70s of the last century, this molecular biologist emigrated to the United States with her husband and two-year-old daughter. They carried all their savings hidden in a teddy bear — about $1,200 at the time.

Since then Karikó worked against the current and without funding. He was looking for a way to turn RNA, a complementary DNA molecule that does almost all of life's work, into a therapy. In 2005 he demonstrated with his colleague at the University of Pennsylvania Drew Weisman that modifying a single letter in the sequence of messenger RNA allows this molecule not to cause a powerful immune reaction. A few years later, Moderna and BioNTech based their messenger RNA immunizations against covid on this finding, achieved in record time.

An RNA vaccine achieves a first success against pancreatic cancer, the deadliest tumor

The first thing that surprises Karikó is the humility he transmits from the first sentence of the interview, held in Madrid, where he received the Commemorative Lesson Award from the Conchita Rábago de Jiménez Díaz Foundation. The scientist says with resignation that since 2020 she has been given more than 100 awards and that her journey around the world will continue for several months, among other things to be invested with honorary doctorates by Harvard and Princeton, two of the best universities in the world. During her career, however, Karikó did not become a professor at her own university. In fact, the institution was on the verge of demoting it because it could not get funds and missold its patents on messenger RNA. Karikó has resigned from her position as vice president of BioNTech, a company to which she will remain linked as an advisor; and explains that a new stage of his life begins. She is one of the strongest candidates to win the Nobel.

Question. After so long working out of the spotlight, how do you feel now with so many accolades?

Answer. I just assume that's what it takes. You will do your job writing this interview and together we will try to educate the population, which is the important thing. We have to find a way to explain complex issues and capture the attention of young people. There are fewer and fewer who want to do science. It is hard work, which does not respond to schedules. The main satisfaction is to come to understand essential concepts. It's something you don't understand until you try, and fewer and fewer kids do it. They prefer quick money, but they don't know that money won't give them happiness.

Q. Have you been happy?

A. Immensely. I felt like a winner. The success was to progress in the experiments: to find a way to produce more protein with RNA, modify the sequence and make it work better, see that it works in animals. The only problem was that I couldn't get funding. They tried to demote me four times. If they hadn't, I wouldn't be who I am. Pitying and licking wounds is useless. The only thing that matters is the next step you take.

Q. What will be your next step?

A. I'm not going back to academic research because I've never succeeded in that world. The University of Pennsylvania retired me 10 years ago, although they keep me with the title of adjunct professor. I don't work there anymore. Now I begin a new chapter of my life. Obviously, I am afraid that it will be the last. At BioNTech I have my own team. I continue to collaborate with them in the development of clinical trials, but only as an advisor. They already know what they have to do and they also have the money to get it.

Q. After the covid vaccines, what will be next?

A. Before the pandemic, both Moderna and BioNTech were already working on a messenger RNA vaccine against the flu. This will probably be the next one, along with the respiratory syncytial virus, which Moderna is developing. This company also has two ongoing trials of a vaccine against HIV and also against the Epstein-Barr virus, which could be the cause of multiple sclerosis. There is also a new experimental vaccine against nipah [an emerging virus in Asia that has a mortality of between 40% and 75%]. It is interesting that both Moderna and BioNTech have announced that they are developing RNA vaccines against shingles. There is already one, but it costs about 800 euros. The advantage of messenger RNA vaccines is that they are cheap and can be developed very quickly.

Katalin Karikó and Tom Hanks embrace after being awarded honorary doctorates by Harvard University (USA). Associated Press/LaPresse (APN)

Q. Do messenger RNA vaccines only have applications against viruses?

A. Nope. They can also be very useful against infections caused by bacteria. There is an experimental vaccine in development against borreliosis, which is transmitted with the bite of a tick, and another against tick-borne encephalitis. In the latter there is an RNA vaccine in animal testing phase that is based not on immunizing against proteins of the pathogen, but against proteins that are in the saliva of ticks, so that they generate immunization from the moment the insect bites. And then we have the messenger RNA vaccine against malaria.

Q. A few days ago BioNTech presented promising results of an RNA vaccine against pancreatic cancer, the most lethal.

R. Companies pioneering messenger RNA vaccines, such as Curevac, founded in 2000, and BioNTech, in 2008, began looking for cancer immunizations. It's a long scientific process that corrects itself as new results come to the human immune system and the complexity of cancer. The latest results from BioNTech have shown that if the patient has an operable tumor, it is possible to develop a vaccine against epitopes [proteins] unique to the tumor. This is an advance because it was thought that in this tumor it was impossible. But the treatment only worked in half of the patients.

Q. Do you know why?

A. Nope. It should be noted that the 16 patients in this clinical trial had gone through several rounds of treatment with various drugs. The vaccine was basically their last chance. His immune system was already very weak, although it was still functioning. What we needed was to generate immunity mediated by killer T lymphocytes [a kind of white blood cell]. Eight responded, and 18 months later they didn't see their cancer recur. Eight others were unresponsive and relapsed. One of the patients who responded had metastases and yet his tumors disappeared. We don't know why. We did see that patients who didn't respond had slightly larger tumors. This is an initial trial with few patients, so we can't generalize. Now we have to keep accumulating information and understand why some people react and others don't. That's science.

Q. A few weeks ago, a Moderna executive predicted that some cancer vaccines could be ready in five years, and BioNTech's founders also made similar statements.

A. No way. No one should say such things. Cancer is too complex. Each type of tumor has its specificities. These predictions are very harmful to people with cancer. It's playing with their hope. When I started at BioNTech in 2013, lung cancer was practically a death sentence. Then came checkpoint inhibitor immunotherapy, which got more and more people to survive this tumor. Now there are still tumors that are invisible to the immune system and we need more research to know why. The good news is that there is now a lot of money for the development of new vaccines and messenger RNA-based treatments.

Q. Could messenger RNA help cure Alzheimer's and other neurological ailments?

A. The problem with messenger RNA is that, no matter how well you wrap it and encapsulate it, it is very difficult for it to cross different tissues, different layers of cells. As soon as it finds a cell, it picks it up, reads its instructions and makes a protein out of them. That is why it is very useful when you need to secrete a certain protein, such as the coronavirus spicule. But if it's about replacing a protein that's already there [Alzheimer's is associated with the accumulation of two dysfunctional proteins, amyloid and tau], RNA can't help. We did the test by introducing it into the cerebrospinal fluid of mice and saw that the messenger RNA never reached the neurons. It is difficult to bring the treatment to neurons threatened by Alzheimer's or Parkinson's. I'm not saying you can't, but a lot of research is needed. That said, effectiveness has been seen in the spinal cord. And also in the treatment of amyloidosis and heart failure.

Q. His daughter, Susan Francia, is a rower and won two Olympic medals with the United States. You compare science with this sport.

A. Have you noticed that you row with your back to the direction of travel? So is science. You don't know where you're going. You don't even know there's a goal. You just know you have to keep going.

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Source: elparis

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