Maria Ormhøj

Project title

RESCUE: Resensitizing cancer cells to CAR T-cell-mediated killing using engineered de novo  protein inhibitors

What is your project about?

CAR T-cell therapy is a groundbreaking form of immunotherapy in which a patient’s own immune cells are engineered to recognize and destroy cancer cells. While this treatment has shown remarkable success in blood cancers, many patients eventually relapse because cancer cells develop mechanisms that make them resistant to immune attack.  

In this project, we will investigate how cancer cells evade CAR T-cell killing and develop new strategies to overcome this resistance. By combining advanced analyses of patient samples with the design of novel protein therapeutics, we aim to identify and block the mechanisms that protect cancer cells from destruction.

Our goal is to create next-generation CAR T-cell therapies that not only recognize cancer cells but also restore their sensitivity to treatment. Ultimately, this could improve outcomes for patients with aggressive blood cancers.

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

My interest in cancer research is both personal and scientific. When my mother was diagnosed with cancer during my teenage years, I experienced first-hand the profound impact the disease has on patients and their families. This sparked my desire to contribute to the development of new treatment options.  

During my studies, I became fascinated by the immune system and its central role in human health. I was particularly fascinated by the delicate balance between protection and harm: the same immune system that protects us from infections and cancer can also contribute to disease when this balance is disrupted. I was fascinated by the idea that the immune system could be harnessed to fight disease, and I quickly realized that this was the direction I wanted to pursue as a researcher.  

Since then, my research has been driven by the ambition to understand and improve cancer immunotherapies. My motivation is to develop new treatments for patients with limited therapeutic options. My dream is to take my own research ideas all the way from the laboratory to patients, to improve and save lives.

What are the scientific challenges and perspectives in your project?

One of the greatest challenges is that we still have only a limited understanding of the mechanisms cancer cells use to survive CAR T-cell attack. Resistance is often complex and varies between patients, making it difficult to develop universal solutions.

In this project, we combine analyses of patient samples with artificial intelligence-driven protein design to develop novel protein binders that can block key cancer cell survival mechanisms. The project is ambitious because it aims not only to identify new forms of resistance, but also to develop concrete solutions that can be translated into future therapies.

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

If successful, our work could make CAR T-cell therapy more effective, allowing more patients to achieve long-term disease control or even cure. At the same time, the principles developed in this project could be applied more broadly within immunotherapy and other targeted treatment strategies.  

In the long term, I hope this research will contribute to a shift from one-size-fits-all cancer treatments towards more precise and personalized therapies tailored to each patient’s disease and resistance mechanisms.

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

The Sapere Aude grant provides me with a unique opportunity to establish and expand my own research group. Beyond enabling an ambitious research programme, it will allow me to develop as an independent research leader.  

For me, Sapere Aude is a crucial step towards building an internationally recognized research environment in cell therapy. It will also enable me to introduce advanced protein design technologies into my research programme and establish a unique research niche at the interface of immunotherapy, synthetic biology, and protein engineering. At the same time, the programme provides access to a strong network of talented researchers across disciplines and offers a unique opportunity for both professional and personal development.