Professor Morten Nielsen

Computer models pave the way for efficient cancer vaccines

Medicine and medico technology Biological systems Cells Genes and genomes Computer calculations Mathematical modelling

Professor Morten Nielsen, DTU Health Tech, develops algorithms and models that are essential for creating better cancer vaccines and medicine.

According to WHO, cancer is one of the primary causes of death worldwide. In 2020, almost 10 million people died from cancer globally, and in Denmark, statistics show that one out of three will get cancer before they reach the age of 75.

Fortunately, more and more people survive a cancer diagnosis. To keep this trend up, we must continuously improve our knowledge of how the immune system functions. The better we understand it, the better we are able to treat illnesses such as cancer.

“We know that patients respond differently to any given disease and the subsequent treatment. The difference originates from our immune system, which is individual for every single person, and affected by nature as well as nurture. On the one hand, our genome bears immense importance for how we respond to different diseases, and on the other hand, previous infections and bacteria we have been exposed to also affect our immune system”, Morten Nielsen explains.

"Our models can predict how the individual patient will react to a given treatment"
Professor Morten Nielsen

Computer models predict the patient’s reaction

For the last 15-20 years, researchers have been able to make computer models that can model and predict how each individual patient will respond to a specific infection and treatment based on the patient’s genome.

Professor Morten Nielsen has contributed significantly to this research field with his research in immunoinformatics and machine learning.

“With our computer models we can understand and describe the differences between your and my immune system with high accuracy based on knowledge about the individual person’s HLA molecules (Human Leukocyte Antigen), and our models can predict how the individual patient will react to a given treatment”, Morten Nielsen says.

Every person has different HLA molecules that influence our individual immune response. This means that efficient treatment will differ from person to person. I.e. for every patient we have a unique pattern, and the computer models can help predict this pattern. Read more about HLA molecules and our immune system below this article.

Towards better cancer vaccines

Morten Nielsen explains that his computer models play an important part in the development of cancer vaccines. The idea behind cancer vaccines is to boost the immune system, and teach it to recognize and focus all of its powers to fight the specific cancer. In principle, a cancer vaccine consists of peptides, which are small pieces of broken down protein with the cancer mutation inside them. However, for the vaccine to be effective, it must be exactly the right peptides, which match the individual patient’s immune response. Here the computer models can assist in choosing the right peptides.

A long way to complete understanding

”Cancer vaccines are going to be an outstanding treatment for cancer, if we can make them work as intended”, Morten Nielsen says, and continues, “We have only understood maybe 1/3 of what defines the human immune response. There are many more components. For example, many different peptides can bind to HLA molecules to be shown on the surface of a cell. However, it is only specific peptides, which provide the correct immune response. Why that is, we do not know. When you develop a cancer vaccine, it is easy to imagine that the incorrect peptides are chosen, which do not give the wanted strong immune response. Quite a few of the existing cancer vaccines are only effective on a few percentages of the patients, and we do not know why. There is still a long way to go”, Morten Nielsen reasons.

Yet, the professor is optimistic, and fully believe that we can achieve a much more complete understanding of our body and immune response. We just need to keep up the work in the field and apply digital solutions. He says, “The greatest challenge, in my point of view, is to understand the difference between the peptides that give a strong immune response and those that do not. What drives the T-cell, when it scans the surface of the cells for mutations, and why does it choose one peptide over another? You can compare it to travelling to the Moon versus travelling to Mars. We have already succeeded in going to the moon, which is a major accomplishment in itself, but put into perspective, it is only a very small step compared to setting foot on Mars”, the professor finishes.

Photo: Professor Morten Nielsen (Photo by: Jesper Scheel)

About the immune system

The immune system exists in our body fluids, i.e. outside the cells, where it is dependent on getting knowledge passed on about any problems inside the cells that needs to be fought. The Human Leukocyte Antigen (HLA) molecules help with this task by showing a kind of snapshot of what is going on inside the cell. The HLA molecules exist on the surface of all cells. When the proteins of the genome is broken down in the cell to peptide fragments, they bind to HLA molecules and are then visible on the surface of the cell.

Cancer cells have mutations in their genome, which for example means that cell division happens too frequently. These characteristic mutations, which are not present in healthy cells, can be read on the surface of the cell by the T-cells. T-cells can be described as the soldiers of the immune system. They react when they discover something unfamiliar in the body and sound the attack. Even though our immune system generally is terrific at finding and fighting harmful mutations, in some instances, cancer cells remain unrecognised, and we for example develop cancer tumours.

This is where a cancer vaccine will be able to help the immune system fight the cancer. However, the first step is to understand more about how our immune system works.