If a vaccine can reduce the severity of Covid-19 in a person infected with the virus that causes it, why can’t the same be achieved with cancer, which kills some 10 million people a year?
In a few months, oncologist Eduardo Vilar-Sánchez will test exactly this theory when he trials a vaccine for hereditary colon tumors that could benefit the general population.
A graduate of Barcelona’s Vall d’Hebron Hospital, Vilar-Sánchez works in the department of Clinical Cancer Prevention at the MD Anderson Cancer Center (Houston, USA) where he studies rare diseases caused by genetic mutations that 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 (an inherited colon cancer), who have a 100% chance of developing the same tumor before their 30th birthday.
Vilar-Sánchez hopes the vaccine he is developing for Lynch syndrome can also help prevent cancer in others. He spoke to EL PAÍS following a recent symposium of the Spanish Association of Human Genetics.
Question: Scientists have been researching cancer vaccines for decades. Why hasn’t one been found?
Answer: We do have vaccines against cancers brought on by viruses, such as human papilloma or hepatitis C. In these cases, the virus is a foreign entity, so it is much easier to create a vaccine.
By contrast, cancer cells come from ourselves; they are more like our own cells than anything else. To develop a vaccine, we look for a particular protein that is expressed in the cells of the cancerous tumor, but we have to be very sure the vaccine does not get into any other organ because we can cause a deadly autoimmune reaction.
Q. If it’s so complicated, why keep trying?
A. Before, we had to research gene by gene, protein by protein. Now, with massive genome sequencing techniques, we can see everything at once and look for those abnormal proteins that are exclusive to the tumor. These massive analyses of proteins were not possible until a few years ago.
Even so, cancer has a thousand faces – colon cancer for example is nothing like brain or bladder cancer. Finding a generic vaccine to try to intercept all cancers is very, very challenging.
Q. How does your vaccine work?
A. When our cells replicate naturally, 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, the copy errors of the replication process are not corrected. They end up accumulating a series of mutations that produce an abnormal peptide, which is a molecule that does not exist in normal tissues. This gives us an opportunity to develop a vaccine.
A. We looked for peptides shared by the majority of patients; people who have had tumors of the colon, endometrium, stomach, or urinary tract. This summer, together with Nouscom, the company that has developed the vaccine, we are going to start the first phase of trials with some 45 patients.
Q. If proven effective, could this vaccine also serve the general population?
A. For a rare disease, the prevalence of Lynch syndrome is considerable: in the US alone there are one million patients. In general, 15% of people with colon cancer [i.e. not just those who have Lynch syndrome] also have damage to their DNA repair system, as do 20% of people with endometrial cancer and 5% with bladder and stomach cancer. If the vaccine [for Lynch syndrome] could be extrapolated [to the people in these situations], yes, it could potentially benefit many people who do not have the hereditary disease.
Q. And this vaccine is capable of preventing cancer before it appears?
A. Colon cancer develops from a polyp, which is a collection of premalignant cells. Sometimes the immune system identifies them and eliminates them. Other times, it does not turn into a tumor. The key is to look for the abnormal proteins in the polyps that do give rise to tumors, and [target them with the vaccine, through which] either the immune system freezes the growth of that polyp or eliminates it.
Q. You lead a project to define what precancer is. Tell us about it?
A. Thanks to projects such as the Cancer Genome Atlas, we now know about mutations in different tumors. We are yet to know which mutations are present in a ‘premalignant [pre-cancerous] lesion’, such as a polyp – perhaps this is where we will find the answer to stopping the development of a tumor using vaccines or chemical compounds.
In the US, the National Cancer Institute (NCI) is doing something very similar in [researching vaccines for] tumors of the respiratory tract and digestive system.
The future of curing cancer lies in prevention. We are already greatly increasing survival and quality of life with current cancer treatments. There are tumors that, thanks to immunotherapy, are treated successfully, but the reality is that the cure will only come through prevention with vaccines or drugs. The [NCI’s] precancer atlas is a preliminary step to achieve this.
Q. Do you think there will one day be preventive vaccines against cancer?
A. I want to be [cautiously] optimistic: much progress is being made, and rapidly; there are more resources right now with the explosion in immunology that has occurred with covid. I think we will see them [preventive vaccines] – there will be very specific vaccines for each tumor.
Q. As a specialist, how do you explain the increase in cases of colon cancer among young people?
A. The problem is that screening strategies help to detect classic, so to speak, colon cancer – the one we know best and that appears at older ages – very well. [But now], early-age cases are growing a lot.
There is a lot of interest in this. We have a project in our hospital analyzing the molecular characteristics of [cancerous colon] tumors in young people. For now, at this molecular level, we do not see clear features [that distinguish the early-age cancers from those that occur in older age].
I think that this spike [in cases of colon cancer among younger people] is actually explained by our sedentary lifestyle in Western economies, and how our food is generated; how we feed ourselves.