The enormous cancer challenge of messenger RNA vaccines, the oncologist: “They are likely to become a new weapon”

The enormous cancer challenge of messenger RNA vaccines, the oncologist: “They are likely to become a new weapon”
The enormous cancer challenge of messenger RNA vaccines, the oncologist: “They are likely to become a new weapon”

Until recently, no one knew them. Except for the researchers who have been studying them for years to identify a keystone for the treatment of cancer and HIV. Then they landed forcefully on the pages of pandemic news and we all got to know them a little closely and very closely. They are the mRna – or messenger RNA – vaccines used by Pfizer BioNTech e Modern to combat the Sars Cov 2 virus. Recently in an interview on Repubblica, Sahin and Tureci, the founders of BionTech, stated that the company is at an advanced stage of clinical trials on groups of volunteers to develop some vaccines against solid tumors, melanoma and colorectal cancer in the future. With the possibility of having them on the market within 4-5 years.

“The immunological system, through its components, day by day, does its job: it recognizes everything that is foreign in our organism and tries to eliminate it”, explains Dr. Giovanni Apolone, scientific director of the Tumor Institute of Milan. “This applies to external elements, such as viruses and bacteria, but also to the cells of our organs that alter, become different, such as cancer cells. Some components of our immune system are cells that produce ‘weapons’, antibodies, which attack foreign elements and maintain the memory of doing so with each new contact. The hypothesis on which many groups in the world had already been working for some time, especially in the oncology field, was precisely this: identify specific elements of the tumor and teach our immunological system to activate a response that eliminates cancer cells. This through the introduction into our cells of a small molecule, the messenger RNA, which is able to instruct them to produce a specific characteristic of the target of interest, the tumor cell, so that when it appeared it would find our organism ready. to react. This technology has now been used in billions of people for Covid, and by now we know a lot about its action, efficacy and safety, superior to traditional vaccines that instead use live, attenuated viruses or their fragments. It should be remembered, however, that there are already more ‘traditional’ vaccines againstHpv (cervical and head-neck cancer) e l’antiepatite B (liver tumor) “.

Doctor Apolone, what are the main problems to be solved in the search for a vaccine against cancer?
“After more than 20 years of research and on the experience derived from vaccines for Covid-19, we are trying to identify some characteristics of the genetic heritage of tumors that are present in all cancer cells, therefore a specific common denominator to be used as target by teaching the cells of the immunological system to produce it through an mRna introduced with a vaccine formed by an inactive vector, so that our cells produce this small part similar to that of the tumor and keep its memory ”.

Having obtained this result, what happens if a cell turns into a tumor?
“This specific part of it will be recognized and then attacked and eliminated through the antibodies produced. We are therefore talking about a ‘preventive’ vaccine “.

BioNTech said it is also working on identifying a patient-calibrated vaccine that targets twenty individual tumor-specific antigens.
“In fact, attempts are also being made to customize the vaccine for a specific tumor in a specific person, in order to use it in the presence of the disease as a ‘therapeutic’ vaccine. These two approaches, the preventive and curative which can also be combined, are in the experimental phase 1, ie the first administrations in volunteers after having passed the phase in the laboratory and in the animal “.

A targeted vaccine for the individual patient is a huge challenge.
“The difficulties are due to the intrinsic heterogeneous nature of tumors which means that even in a single tumor mass the cells have a varied genetic and molecular patrimony that changes over time, thus generating new subspecies, which we could define variants, which could become so different that they are resistant to the vaccine. A phenomenon that we have already observed during the administration of current anticancer therapies: at the beginning the tumor is reduced, to the point of disappearing; then develops a resistance to the appearance of cells that are no longer sensitive to the drug in question, the disease progresses or recurs by imposing a new line of treatment. Future studies will allow to verify if this phenomenon will be present and to try to take the necessary measures. It is likely that the new cancer vaccines will become another new weapon in our fight against cancer, to be used sequentially or in combination with the other therapies we now use, namely surgery, radiotherapy and various anticancer drugs. We know a lot and will learn a lot during the various ongoing and future studies and projects, but it is certainly a line of research that will produce evidence, knowledge and new preventive and therapeutic approaches ”.

With Covid vaccines, States are confronting the dilemma of the high costs to be incurred. Is an even greater economic challenge to be expected for such targeted vaccines?
The costs of the research, now well funded in light of the results obtained against Covid 19 and then of vaccines, are and will be very high. Not so much the individual cost of the final medicine (from a few tens to a few hundred euros), but the overall cost for each individual State as preventive and / or therapeutic vaccines should be administered to hundreds of thousands if not millions of citizens and patients. In Italy there are millions of people at risk of cancer due to incorrect lifestyle habits such as smoking and about 370 thousand new cases a year “.

Could the prospect of having vaccines that intervene in various serious pathological pictures induce people to follow a lifestyle without particular health precautions?
“This is a dilemma that could become an opportunity: most cancers, especially the most frequent ones such as those of the lung, are linked to our lifestyle and bad habits (sedentary lifestyle, smoking, alcohol, overweight, etc.). The availability of a preventive vaccine could reduce attention to the correction of these factors which are the cause or the contributing cause of the disease. However, this aspect opens up a debate on the ethics of allocating important resources of our health systems to a disease that could be prevented with less expensive and more natural approaches, for example by avoiding the consumption of tobacco “.

How do you deal with this dilemma?
“In reality, the debate is already underway. I return to the example of smoking which causes about 200 deaths every day in Italy due to its carcinogenic effect and on the circulatory system (respectively second and first cause of death in Italy). A lung cancer screening and early diagnosis program is starting in Italy, the RISP Project, funded by the Ministry of Health and coordinated by the Milan Cancer Institute of Milan, a project that provides for the execution of a periodic CT scan at people at risk of developing cancer, i.e. smokers; alongside the tac, a cessation program will be offered, also through the use of specific drugs. We can therefore think that vaccination programs against cancer could be coupled with primary prevention campaigns offered with preventive vaccination ”.

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