Morten Orebo Holmström

Project title

Harnessing mechanisms of cellular Immunity to improve outcomes after allogeneic hematopoietic stem cell Transplantation for MyElofibrosis (HIT-ME)

What is your project about?

This project focuses on myelofibrosis, a chronic type of blood cancer that represents an advanced stage of chronic myeloproliferative neoplasms (a group of chronic blood cancers). The only curative treatment is a bone marrow transplant from a healthy donor. A bone marrow transplant works because the donor's immune system attacks and kills the cancer cells in the patient. Unfortunately, a significant number of patients experience a relapse of their myelofibrosis and die from it. The purpose of this project is to investigate how to increase the immune system's ability to recognize and kill the myelofibrosis cancer cells. Through laboratory analyses, we will examine whether it is possible to vaccinate against a specific protein in myelofibrosis – a protein known to inhibit immune function. At the same time, we will perform a detailed analysis of the immune system's function and composition following the bone marrow transplant. The goal is to identify key characteristics of the immune system in patients who are successfully cured by the transplant.

How did you become interested in your particular field of research?

As a medical doctor, I have always been deeply fascinated by both the destructive and healing powers of the immune system. In fact, there are very few diseases or conditions where the immune system does not play a role. Therefore, when I graduated as a physician, I chose the field of hematology, which is the study of cancers in the blood and lymphatic organs – essentially, cancer of the immune system. After a few years as a hospital physician, I entered the laboratory, where I used cell experiments to investigate the possibility of vaccinating patients with chronic myeloproliferative blood cancer against their disease. I was instantly hooked the moment I stepped into the laboratory and was allowed to work with immune cells, getting very close to the actual biology. I find discovering and describing new things extremely stimulating, and that is exactly what working as a scientist allows. My laboratory results enabled two clinical trials in patients with blood cancer, which further stimulated my continued work with the immune system. Through more than ten years in the laboratory, I have learned how manipulation of the immune system holds immense potentials to treat and cure patients and I hope that this can be used to help patients with blood cancer.

What are the scientific challenges and perspectives in your project?

We know that the immune system can be used to treat and cure cancer, and this treatment modality – cancer immunotherapy – has revolutionized the treatment of several cancer types over the past 10–15 years. Unfortunately, chronic myeloproliferative neoplasms are not among the diseases that have reaped the benefits from these new developments and discoveries. We know that the functionality of the immune system in patients with myeloproliferative cancer is inferior to the functionality in healthy individuals. Additionally, we know that the amount of cancer cells in these patients is very high, which is an obstacle to the effectiveness of cancer immunotherapy, including cancer vaccination. If we can show that the mechanisms inhibiting the immune system's function can be used as targets for vaccination and simultaneously demonstrate specific characteristics of the immune system in patients with a good outcome after a bone marrow transplant, we can further develop methods to increase the immune system's ability to kill cancer cells after transplantation and thereby improve patient survival.

What is your estimate of the impact, which your project may have to society in the long term?

We want to investigate whether vaccination against a specific immune-inhibiting protein has the potential to increase the activity of the immune system in patients with cancer. As this particular protein is not only produced in elevated amounts in chronic myeloproliferative blood cancer but also in several other cancer types, a vaccine treatment targeting this protein could also be used to activate the immune system in other cancers. Because cancer vaccination causes very few side effects, the vaccine could be combined with other types of cancer treatment to increase their effectiveness. Furthermore, the detailed study of the immune system in patients who have received a bone marrow transplant will benefit patients with other types of blood cancer. Leukemia is a blood cancer closely related to myelofibrosis and is also treated with a bone marrow transplantation. The findings from my research can easily be applied to investigate possibilities for increasing the efficacy of bone marrow transplantation in patients with leukemia.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

Joining the Sapere Aude program will be completely instrumental for me as a researcher and for my research career. With a grant from the Sapere Aude program, I can establish my own independent research team focusing on the interaction between the immune system and cancer, particularly in blood and lymphatic cancers. The research world can be tough and relentless, so I also consider a grant from Sapere Aude as a significant recognition of my research and a major boost to involve myself in more international collaborations.