If a vaccine prevents someone from suffering from severe covid despite being infected, why can’t the same be achieved with cancer, that pandemic that kills 10 million people a year? Oncologist Eduardo Vilar-Sánchez has been pursuing this type of immunization for 10 years. In a few months he will test his most promising prototype on patients.
Vilar-Sánchez works at the MD Anderson Cancer Center in Houston (USA). The name of her department would be surprising in any Spanish hospital: clinical cancer prevention. Its goal is to stop tumors before they appear.
This 42-year-old from Madrid is used to seeing cancer in fast motion. After receiving his doctorate at the Vall d’Hebron Hospital in Barcelona, he went to the United States to study rare diseases caused by genetic mutations They are inherited from generation to generation in the same family. His patients include people with Lynch syndrome who have an 85% chance of developing colon cancer in their lifetime; 17 times more than the general population. The doctor also treats people affected by familial adenomatous polyposis, who have a 100% chance of developing the same tumor before their 30th birthday. The hope of this doctor is that the vaccine he is developing for the first disease can also help the general population.
In this interview, the oncologist —who recently participated in a symposium of the Spanish Association of Human Genetics— transmits hope about the possibility of these vaccines; but “without selling smoke”.
I askeda. Science has been looking for decades cancer vaccines, why haven’t you got any?
Response. It should be emphasized that we do have vaccines against cancer induced by viruses, such as the human papilloma or that of hepatitis C. It is much easier in these cases because the virus is a foreign entity. Instead, cancer cells come from ourselves. They are more like our own cells than anything else. To get a vaccine we look for a protein that is expressed in those tumor cells, but we have to be very sure that it is not in any other organ because we can cause a deadly autoimmune reaction.
P. If it’s so complicated, why keep trying?
R. To search for these vaccines, massive protein analyzes must be carried out. This was not possible until a few years ago. Before we studied gene by gene, protein by protein. Now, with massive genome sequencing techniques we can see everything at once and look for those aberrant proteins unique to the tumor. Even so, cancer has a thousand faces, colon cancer has very little to do with brain or bladder cancer. Finding a generic vaccine to try to intercept all cancers is very, very complicated.
P. What is the approach of your vaccine?
R. When our cells replicate naturally to have daughters they generate a new strand of DNA copied from the original cell. Copy errors are made in this process, but there are systems that correct them with great efficiency. Patients with Lynch syndrome have a deactivated DNA repair system known as mismatch. In these patients many errors remain there. In the end they accumulate a series of mutations that produce an aberrant peptide, a molecule that does not exist in normal tissues. This gives us an opportunity to develop a vaccine.
P. How?
R. We look for the peptides shared by the majority of patients; people who have had tumors of the colon, endometrium, stomach, or urinary tract. This summer we are going to start the first phase of trials with some 45 patients together with the company that has developed the vaccine, Nouscom. In total it contains 209 aberrant peptides.
P. If it proves effective, could this immunization also serve the general population?
R. Be careful, the prevalence of Lynch syndrome is considerable: in the US alone there are one million patients. It is a rare disease, but worldwide the number of patients is significant. But yes, in general, 15% of people with colon cancer also have damage to this DNA repair system. It could be extrapolated to all of them. In endometrium it is 20%. In bladder and stomach, 5%. This can potentially benefit many patients who do not have the hereditary disease.
P. And this vaccine is able to prevent cancer before it appears?
R. Colon cancer develops from a polyp, which is a collection of premalignant cells. Sometimes the immune system identifies them and eliminates them. In others it does not, but the lesion does not turn into a tumor. The key is to look for the aberrant proteins in the polyps that do give rise to tumors, immunize with them, and either the immune system freezes the growth of that lesion or the response is so intense that it eliminates it.
P. You lead a project to define what precancer is. What does it consist of?
R. Right now we already know the mutations that exist in the different tumors thanks to projects such as the Cancer Genome Atlas. It remains for us to know what mutations are present in a premalignant lesion, in a polyp, for example. Perhaps that is where the answer is to stop the development of a tumor using vaccines or chemical compounds. In the US, the National Cancer Institute is doing something very similar in tumors of the respiratory tract and digestive system. The future of curing cancer lies in prevention. With current treatments we are already greatly increasing survival and quality of life. There are tumors that, thanks to immunotherapy, are treated very well, but the reality is that the cure will only come through prevention with vaccines or drugs. The precancer atlas is a preliminary step to achieve this.
P. Do you think there will one day be preventive vaccines against cancer?
R. I think we will have them and we will see them arrive. I want to be optimistic, but without selling smoke. Much and very fast progress is being made. They will be very specific vaccines for each tumor. In addition, right now with the explosion in vaccinology that has occurred with covid, there are many more resources. In the next 5 or 10 years there is going to be tremendous progress.
P. You are a colon cancer specialist. How do you explain the increase in cases among young people?
R. There is a lot of interest in this. The problem is that screening strategies help to detect classic colon cancer very well, so to speak, the one we know best and that appears at older ages. Now the cases are growing a lot at an early age. In our hospital we have a project to understand the molecular characteristics of tumors in young people. For now we do not see clear features at the molecular level. I think that this rebound is actually explained by our lifestyle. How we feed ourselves, how food is generated in Western economies and by sedentary lifestyle.
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