• GRACE PAULS

Updated Saturday, February 4, 2023-18:56

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When SARS-CoV-2 burst into our lives in 2020,

vaccines based on messenger RNA (mRNA)

were already the subject of various trials and publications, several of them aimed at

using this technology in the fight against cancer

.

Preliminary results showed that there was room for hope, but there were still many things to improve and doubts associated with the use of a completely new technology.

Then the pandemic came and everything seemed to fade into the background.

Cancer continued to be one of the great threats, but the saturation of the health system and the exceptional nature of the situation caused

delays in diagnosis and treatment

.

However, the strategy against Covid-19 owes a lot to cancer research, and that is that without the previous years dedicated to researching mRNA vaccines,

it would not have been possible to develop a version against SARS-CoV infection. -2 in such a short time

(it takes between 10 and 15 years to develop a vaccine, but Pfizer and Moderna managed to prove the efficacy and safety of their proposal for Covid-19 in less than a year).

At the same time,

the acceleration in development and its massive application

are a fundamental source of information to resume, with much more data and at a more advanced point, the original purpose.

Why can this technology make a difference?

In the case of contagious diseases, one of its main advantages is that

they are not based on inoculating a virus

(inactivated or part of it), which entails prior culture in the laboratory and a purification process.

mRNA vaccines take advantage of our cellular machinery so that

our own cells produce proteins identical to those carried by the virus on the surface

, so that the immune system trains itself and learns to recognize them so that it is prepared in case of infection to occur.

To do this, it

is necessary to sequence the viral RNA

and locate the part that explains how to produce that protein in question, copy it, and inoculate it into the body so that the cells do the job without posing a risk to the individual.

RNA degrades very quickly and in no case does it affect our DNA

, which remains protected in the cell nucleus.

And since you don't inoculate a virus either, they are a

safer option

.

But if we talk about cancer, the focus has to be different

.

In the first place, and contrary to what happens with viruses, these are

therapeutic, not preventive, vaccines

.

Although the hepatitis B and human papillomavirus vaccines prevent an infection that could lead to a tumor, they are not an example of an approach needed in other cases.

On the other hand,

the enemy to be beaten is more elusive and these vaccines need a clear and defined objective to be effective

.

"These vaccines are designed so that our immune system recognizes some proteins as a threat and attacks them," explains Dr. Rodrigo Sánchez-Bayona, scientific secretary of the Spanish Society of Medical Oncology (SEOM) and oncologist at the 12 de Octubre University Hospital in Madrid, "but in the case of tumor cells, which are cells of our own body that mutate, these cells ultimately share proteins very similar to those of neighboring healthy cells."

The similarity between diseased and healthy cells not only reduces effectiveness, it also poses a risk

.

"It could happen that our immune system attacks healthy cells and produces autoimmune problems," says Dr. Sánchez-Bayona, "To do this, it is necessary to find 'target' proteins that tumor cells have and are not expressed or that do so in a very low proportion in healthy cells".

The key to overcoming this difficulty is also what makes these vaccines so promising.

And it is that the identification of these 'targets' goes through a

personalized study of the patient

, so that mRNA vaccines are emerging as a banner of personalized medicine.

Today it is possible to

sequence healthy cells and tumor cells to be able to compare them with each other and accurately identify the differences

.

We are talking about hundreds, even thousands of mutations, which thanks to computing we will be able to reduce to a more manageable number of possibilities.

It is about identifying the so-called

neoantigens

, those specific for a patient's tumor (it may have unique markers), common in a certain type of cancer or shared among several types.

To do this, it would suffice to analyze the patient's tissues, in addition to having a database that allows comparing profiles.

mRNA vaccines can incorporate up to 34 neoantigens, so they could target several 'targets' at the same time

.

In the era of personalized medicine, mRNA vaccines are a tool to take into account, and also with a

better tolerated side effect profile than conventional chemotherapy

.

"Although immunotherapy can cause reactions such as fever, muscle pain, or joint pain after its administration," explains Dr. Sánchez-Bayona, "the vast majority tend to be mild and transient effects."

We saw it with the Covid-19 vaccines, it is a picture that we already know.

But the advantages do not stop there, the oncologist recalls that vaccines

can generate immunological memory

, so in the same way that we can fight a virus like SARS-CoV-2 after having been vaccinated, our immune system could also be capable of to recognize the threat of cancer in the future if there are relapses with cells that present the same protein, attacking them before it is clinically evident.

The possibility of combining the mRNA vaccine with other immunotherapies

is currently being successfully tested

.

Moderna published a few weeks ago the preliminary results of a clinical trial in patients with stage III/IV melanoma who received both the vaccine and immunotherapy with pembrolizumab.

When comparing the results of this combination with those of patients who had only received pembrolizumab, a 44% reduction in the risk of recurrence or death due to disease was found in the first group.

These are very encouraging data but they still have to be read with caution.

"Although the results are promising," warns the oncologist, "it is still too early to be able to talk about a cure for melanoma."

What is evident is that vaccines allow a greater degree of personalization in treatment than antibody-based immunotherapies, they have a "high specificity", in the words of Sánchez-Bayona.

But at the same time

, these therapies are a very interesting complement

, since "they stimulate the immune system to recognize tumor cells as a threat",

thus enhancing the efficacy of the vaccine

.

There is still a lot of work to be done and problems still to be resolved to be able to include mRNA vaccines among the usual treatments against cancer, such as "long-term safety, knowing the number of doses needed or the optimal time of administration," he recalls. Sanchez-Bayona.

Nor will something be achieved immediately,

times will not be as fast as with Covid

.

Years of work, research and trials remain until these indications translate into tangible success, into a real cure.

And that is if there are no setbacks or dead ends.

It is a long-distance race, but 'thanks' to the momentum caused by the pandemic, today we can glimpse that future a little closer.

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  • Oncology

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