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What mRNA technology can do: Dr. Dietis talks to “P” about the experimental…

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“The mRNA technology in cancer vaccines is similar to that against SARSCov2, as is the general idea: to train our immune system to fight a biological enemy”

A few days ago it became known that in England the vaccination of cancer patients started. Thousands of NHS patients will receive personalized vaccines for skin, bowel and lung cancer over the next year, in what has been described as a “landmark moment” for cancer care. Experts believe that treatments that are specifically designed for patients to stop cancer from coming back will mark a new era in the fight against the disease so that it can one day be used against all cancers. Dr. Nikolas Dietis, assistant professor of Pharmacology at the Medical School of the University of Cyprus, spoke to “P” on the subject. In his interview with “P”, he talks about “personalized vaccines”, mRNA vaccines and the advantages they have compared to other treatments, such as “much fewer side effects compared to conventional chemotherapy”.

What exactly is happening now with cancer patients in England and when are we expecting the first results from these “experimental” vaccinations?

The vaccinations taking place at the moment are part of a clinical trial that started a few weeks ago, based on a collaboration between the British NHS and the company Biontech, where “personalized” vaccines will be given to patients with early-stage colorectal cancer. Patients enter a specially designed platform where their eligibility criteria for participation in the study are examined. The first patient, for example, was a 55-year-old with early-stage colorectal cancer found after a routine test. This particular cancer gives about a 65% 5-year survival rate. After the patient underwent surgery for tumor removal and completed his chemotherapy, he joined the clinical study after checking the relevant platform. The goal of the study is to give vaccines to 10,000 patients by 2030. But I believe that the first preliminary results will start to come out much sooner, after giving the vaccine to a smaller number of patients and after a certain time of examining patients has passed and the first data are analyzed.

“Personalized Vaccines”

We hear that these vaccines are “personalized” . Explain to us a little how a “personalized vaccine” is created-works.

First of all, it is important to mention that there are two types of cancer vaccines, preventive vaccines and therapeutic ones. Preventive vaccines are those that reduce the risk of developing cancer, usually those types of cancer associated with certain infections. For example, human papillomavirus, which is a sexually transmitted virus that can cause cervical cancer, and to prevent infection and the risk of developing cancer we give the HPV vaccine. Another well-known example of a preventive vaccine is the hepatitis B vaccine, where the virus can cause liver cancer and the vaccine can confer significant protection. In contrast, therapeutic vaccines are vaccines that are used as a treatment to reduce either the size of the tumor, the risk of its spread/metastases, or the risk of the cancer coming back. Examples of such vaccines are the T-VEC vaccine given since 2015 for metastatic melanoma, the Sipuleucel-t vaccine given since 2010 against metastatic prostate cancer, but also the recent Adstiladrin given since 2022 against bladder cancer in patients who do not respond to chemotherapy.

Nevertheless, the therapeutic vaccines we had for so many years were not that effective, which is why we don't have many that have passed clinical studies and been approved. In addition, the same type of cancer in different patients can have many genetic differences, which creates the basis for a wide variation in the effectiveness of a drug or vaccine. In short, even if the same drug is given to the same type of cancer, in different patients, there will be variation in the treatment outcome. To solve this problem, we should target the patient's cancer with a drug that is effective for the specific patient, that is, there should be “personalization” in the treatment. This is achieved by the new vaccines, which are based on the mRNA platform. Each vaccine is designed based on the specific patient's cancer profile, based on the mutations and specific antigens it expresses. Thus, when the specially designed, “personalized” vaccine is administered to the patient, its effectiveness is very high.

mRNA vaccines

Based on the evidence that exists so far, in which types of cancer these vaccines can be used and in what way. For example, will the patient only receive the vaccine without needing any other treatment, are we talking about combining the administration of the vaccine with immunotherapy?

mRNA vaccines against cancer have several advantages over other treatments: a) they can theoretically treat any type of cancer, b) we can with relatively great technical ease design personalized vaccines and dramatically increase the treatment effectiveness rate, c) they can be designed and produced quickly and more easily than older vaccines or even conventional drugs, and d) have far fewer side effects than conventional chemotherapy.

Nevertheless, nothing is developed without its own comparative disadvantages: Individualization for each patient takes a long time to do (more than 6 months from the time of starting to design a vaccine for a patient) compared to the treatment plan of a patient. More time means more cost – these vaccines are very expensive since they are only designed for a specific patient. Additionally, mRNA vaccines are based on training our immune system how to deal with cancer, and so its effectiveness is based on the effectiveness of the patient's immune system, which is suppressed by either the cancer or the chemotherapy. This means that these vaccines are more effective for patients who have stronger immunity, and not so much for patients with weakened immunity. Finally, these vaccines are usually more effective in the early stages of cancer and not as effective in advanced stages.

Of course, like all things in medical science, I expect that there will be significant research work in the coming years to improve upon the drawbacks and difficulties currently facing mRNA cancer vaccines. Therefore, in the next 5-10 years I believe we will see not only more cancer vaccines, for more types of cancer, but also with significant improvements in their range of effectiveness.

Result of the coronavirus?

In recent years, mRNA technology has given new impetus to efforts to create therapeutic vaccines for cancer. Is this an idea that was created now, after the coronavirus pandemic? Tell us a little, do the vaccines that are now being given to cancer patients have anything to do with those against the coronavirus?

mRNA technology is not a new technology – it has been used in medical research and biotechnology for over 30 years. Nevertheless, it is true that the SARSCov2 virus pandemic allowed huge and rapid leaps to be made in improving the way mRNA vaccines are designed, the speed of their production, the method of their preparation, etc. All this was done when a lot of money was invested, thousands of scientists were involved and the public and private international research and technology sectors worked together thoroughly, towards the same specific goal. This massive action put us many years ahead and paved the way for us to apply our new knowledge to older problems where we didn't do so well at being effective, such as cancer therapeutic vaccines. There are some important technical differences between pandemic vaccines and cancer vaccines, apart from the obvious difference that pandemic vaccines were preventive vaccines while cancer vaccines are curative. A technical difference, for example, is that pandemic vaccines contained an mRNA sequence (which gave our body information about a specific molecular target against the virus), while cancer vaccines usually contain a mixture of different mRNA sequences where they target different targets expressed by the patient's cancer. Nevertheless, the general mRNA technology in cancer vaccines is similar to that against SARSCov2, as is the general idea: to train our immune system to fight a biological enemy, be it external (e.g. a virus), or internal (like some of our defective cells dividing uncontrollably).

Source: politis.com.cy

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